|
 
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| REVIEW ARTICLE |
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| Year : 2012 | Volume
: 4
| Issue : 11 | Page : 523-532 |
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Antioxidant and anti-inflammatory role of paraoxonase 1: Implication in arteriosclerosis diseases
Dmitry Litvinov1, Halleh Mahini2, Mahdi Garelnabi2
1 Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA
2 Department of Clinical Laboratory and Nutritional Sciences, University of Massachusetts Lowell, MA, USA
| Date of Web Publication | 9-Nov-2012 |
Correspondence Address:
Mahdi Garelnabi
Department of Clinical Laboratory and Nutritional Sciences, School of Health and Environment, University of Massachusetts Lowell, 3 Solomont Way, Lowell, MA 01854, Suite 4, Lowell, MA
USA
 Source of Support: This work has been supported by a startup fund from the University of Massachusetts Lowell for Dr. Mahdi Garelnabi., Conflict of Interest: None  | Check |
DOI: 10.4103/1947-2714.103310
Paraoxonase 1 (PON1) is a hydrolytic enzyme with wide range of substrates, and capability to protect against lipid oxidation. Despite of the large number of compounds that can be hydrolyzed by paraoxonase, the biologically relevant substrates are still not clearly determined. There is a massive in vitro and in vivo data to demonstrate the beneficial effects of PON1 in several atherosclerosis-related processes. The enzyme is primarily expressed in liver; however, it is also localized in other tissues. PON1 attracted significant interest as a protein that is responsible for the most of antioxidant properties of high-density lipoprotein (HDL). Several bioactive molecules such as dietary polyphenols, aspirin and its hydrolysis product salicylate, are known to stimulate PON1 transcription activation in mouse liver and HepG2 cell line. Studies on the activity, function, and genetic makeup have revealed a protective role of PON1. Some striking data were obtained in PON1 gene knockout and PON1 transgenic mouse models and in human studies. The goal of this review is to assess the current understanding of PON1 expression, enzymatic and antioxidant activity, and its atheroprotective effects. Results from in vivo and in vitro basic studies; and from human studies on the association of PON1 with coronary artery disease (CAD) and ischemic stroke will be discussed. Keywords: Antioxidants, Atherosclerosis, Cardiovascular disease, Coronary artery disease, PON1
How to cite this article:
Litvinov D, Mahini H, Garelnabi M. Antioxidant and anti-inflammatory role of paraoxonase 1: Implication in arteriosclerosis diseases. North Am J Med Sci 2012;4:523-32 |
How to cite this URL:
Litvinov D, Mahini H, Garelnabi M. Antioxidant and anti-inflammatory role of paraoxonase 1: Implication in arteriosclerosis diseases. North Am J Med Sci [serial online] 2012 [cited 2023 Apr 2];4:523-32. Available from: https://www.najms.org/text.asp?2012/4/11/523/103310 |
| PON1 Enzymatic Activity and Antioxidant Effects | |  |
Paraoxonases were originally discovered as enzymes hydrolyzing exogenous toxic organophosphate compounds such as insecticide paraoxon. There are three members of paraoxonases family currently known: Paraoxonase 1 (PON1), Paraoxonase 2 (PON2), and Paraoxonase 3 (PON3), which are encoded by three separate genes on the same chromosome 7 (human) or chromosome 6 (mouse). PON1 protein consists of 354 amino acids with molecular mass 43 kDa. [1] All three human members of the family are 70% identical at nucleotide level and 60% identical at the amino acid level. [2]
Studies on enzymatic activity of paraoxonases revealed esterase and lactonase/lactonizing activities in addition to organophosphatase activity. [3],[4] Despite of the large number of compounds that can be hydrolyzed by paraoxonase, the biologically relevant substrates are still not determined for certain. In many cases arylesterase activity is measured to access PON1 level in biological samples. Based on kinetic parameters of paraoxonases toward different substrates, it is assumed that lactones are the likely physiological substrates. [4] Hydrolysis of homocysteine thiolactone by PON1 is considered to be protective against coronary artery disease (CAD). [5]
After the introduction of the oxidative stress hypothesis of atherosclerosis and the discovery of antioxidant effect of high-density lipoprotein (HDL), [6],[7] PON1 attracted significant interest as a protein that is responsible for the most of antioxidant properties of HDL. [8] Purified PON1 protects HDL and low-density lipoprotein (LDL) from oxidation catalyzed by copper ions. [9],[10] PON1 inhibits copper-induced HDL oxidation by prolonging oxidation lag phase, and reduces peroxide and aldehyde content in oxidized HDL. Remarkably, PON1 inhibitors PD-11612, PD-65950, PD-92770, and PD-113487 lessen this antioxidative effect of PON1. Incubation of purified PON1 with hydrogen peroxide or lipid peroxides partly decomposes them. PON1 is especially effective in decomposition of linoleate hydroperoxides. [9] Also, mass-spectrometry analysis of biologically active fraction of oxidized2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC) underwent PON1 treatment showed degradation of these oxidized phospholipids by PON1. [11]
The exact antioxidant mechanism of PON1 is not known yet, although it is known that protection is not caused by chelating of copper ions or because of potential lipid transfer from LDL to HDL. Existence of an enzymatic mechanism is supported by the observation that heat inactivation of purified PON1 abolishes its antioxidant effect. [10]
Some in vitro data suggest that antioxidant activity might be related to other components of purified PON1 preparations. [3],[12] However, experiments with PON1 deficient mouse provide strong evidences that PON1 is required to enable HDL antioxidant properties. HDL from PON1 knockout animals were more prone to oxidation and were less efficient in the protection of LDL from oxidation in co-cultured cell model of the artery wall compared with HDL from control mice. [13] Also, transfection of PON1-deficient peritoneal macrophages (isolated from PON1 knockout mice) with human PON1 decreased level of peroxides, lowered release of superoxide, and increased intracellular level of reduced glutathione, key observations are summarized in [Table 1]. [14] | Table 1: Summary of key facts on PON1 expression, activity, and effects in in vitro and in vivo studies
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| PON1 Expression and Tissue Distribution | | |
Liver is the principal tissue for PON1 gene expression. The first PON1 messenger ribonucleic acid (mRNA)ionanalysis in different rabbit tissues was performed by northern blot, and revealed PON1 mRNA expression predominately in liver. [15] Polymerase chain reaction (PCR) amplification using a panel of first-strand complementary deoxyribonucleic acid (cDNAs) from 24 tissues detected PON1 expression in kidney and colon beside liver and fetal liver expression. [16] Biopsies showed PON1 mRNA and protein expression in human but not in mouse gastrointestinal tract. [17] Deletion analysis in cultured cells revealed that cell type specific expression in liver and kidney is determined within first 200 bp of promoter area. [18]
There are several transcription factors and pathways that regulate PON1 expression [Figure 1]. | Figure 1: Pathways and transcription factors that involved in transcriptional regulation of PON1 expression in liver. All processes occur in liver, and bile acid -stimulated synthesis of fibroblast growth factor 19 (FGF-19; or FGF-15 in mouse) might be additionally occur in ileum. Positions of regulatory elements are shown based on PON1 gene in human. Arrows represent activation effect. Signals from PMA (phorbol 12-myristate 13-acetate) and high glucose activate transcription factor Sp1 through protein kinases C (PKC) and p44/ p42 mitogen-activated protein kinases (MAPK)
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A ubiquitous mammalian transcription factor Specificity Protein 1(Sp1) plays an essential role in regulation of PON1 expression. High glucose level activates protein kinase C (PKC), which activates Sp1, and stimulate PON1 transcription in human hepatoma cell lines HepG2 and HuH7. [19] A potent PKC activator phorbol 12-myristate 13-acetate (PMA) also stimulates PON1 transcription in HepG2 through activation of Sp1. Two members of PKC family are involved, PKCz (zeta) and PKC-α (alpha) activation. PKCz (zeta) mediates transcriptional upregulation PON1 in HepG2 in response to insulin. [20] Statins (pitavastatin, simvastatin, or atorvastatin) stimulate PON1 transcription through Sp1 activation as well, however, they activate another kinase, p44/p42 mitogen-activated protein (MAP) kinase, as was observed for pitavastatin in HuH7 cells. [21],[22] Also, pivostatin-stimulated p44/p42 mitogen-activated protein kinase (MAPK) activates sterol regulatory element binding protein 2 (SREBP-2), which contributes to transcriptional activation of PON1. Simvastatin activates SREBP-2 and upregulates PON1 as well. [22],[23]
Dietary polyphenols, such as resveratrol, aspirin and its hydrolysis product salicylate, and artificial ligands of aryl hydrocarbon receptor (AhR), such as 3-methylcholanthrene, activate AhR and stimulate PON1 transcription activation in mouse liver and HepG2 cell line. [24],[25],[26] c-Jun is another transcription factors that is involved in PON1 expression. The activity of c-Jun is regulated by c-Jun N-terminal kinase (JNK). Phosphorylated c-Jun in a complex with c-Fos or some other transcription factors forms an active AP-1 complex that usually promotes transcription of target genes. Thus, berberine (benzyl tetrahydroxyquinoline), a cholesterol lowering alkaloid, activates JNK, c-Jun and stimulates PON1 transcription in human hepatoma cell lines. [27] However, stimulation of JNK/c-Jun pathway by bile acids leads to opposite effect. Bile acids such as taurocholate, cholic acid, or chenodeoxycholic acid inhibit PON1 expression in liver of C57BL/6J mice, and in HepG2 and HuH7. The inhibition of PON1 expression starts with activation of farnesoid X receptor (FXR) by bile acids that promote expression of fibroblast growth factor 19 in human (FGF-19) or FGF-15 in mouse. The growth factor activates fibroblast growth factor receptor 4 (FGFR4) followed by activation of JNK, and phosphorylation of c-Jun. Opposite to activation of c-Jun by berberine, FXR/FGF-19/FGFR4/JNK/c-Jun pathway results in suppression of PON1 transcription. FXR and FGFR4 are absolutely necessary for the pathway. Bile acids do not inhibit PON1 expression in FXR-/- and FGFR4-/- mice. [28],[29]
Paraoxonase activity in human liver is primarily localized in microsomal fraction. [30] It is likely that PON1 stays associated with endoplasmic reticulum through its hydrophobic N-terminus until it is released from the hepatocytes. The mechanism of PON1 secretion is not well investigated. A study on cultured hepatocytes and transfected Chinese hamster ovary (CHO) cells, which do not naturally express PON1 and ApoA proteins, shed some light on releasing of PON1 from the cells. When PON1 protein is synthesized, it accumulates on plasma membrane and slowly dissociate into extracellular medium. Dissociation is promoted by HDL, very-low-density lipoprotein (VLDL), and in much lesser extent by protein-free phospholipids particles or ApoA-I protein. LDL does not promote PON1 release from the cells. [31],[32]
PON1 binds to HDL through interaction of hydrophobic N-terminus to phospholipids, and through PON1-ApoA interaction. [33] ApoA protein composition of HDL is essential for binding to PON1 protein. Two major principal HDL proteins, that is, ApoA-I and/or ApoA-II which differ in their properties are linked to atherosclerosis modulation. Thus, transgenic mice with HDL consisting of both human ApoA-I and ApoA-II developed 15-fold greater lesions compared with mice with HDL containing solely human ApoA-I. [34] In vitro study of reconstituted HDL demonstrated that ApoA-I containing HDL stabilizes PON1 binding as compared with protein-free HDL particles, and ApoA-II in opposite destabilizes the HDL-PON1 complex. The paraoxonase and arylesterase activities of PON1 do not depend on the apolipoprotein content of HDL. However, ApoA-I containing HDL significantly increases lactonase activity of PON1, promotes inhibition of LDL oxidation, and stimulates macrophage cholesterol efflux compared with ApoA-II containing HDL. [35],[36] A study of human HDL isolated from ApoA-I deficient patients revealed that PON1 is still associated with HDL in the absence of ApoA-1, however, the PON1-HDL complex is less stable, and PON1 loses activity faster than in normal controls. [37]
Similar effects of ApoA protein composition in HDL were observed in transgenic animal studies. A higher content of human ApoA-II protein in mouse HDL suppresses PON1 binding to HDL compared with HDL with lower human ApoA-II content. HDL high in human ApoA-II binds less PON1 protein, possesses less PON1 activity, and is impaired in protection of LDL from oxidation. Transgenic mouse with higher human ApoA-II content in HDL are more susceptible to atherosclerosis compared with transgenic animals with lower ApoA-II level in HDL and control animal. [34],[38],[39]
HDL facilitates distribution of PON1 protein through the body. HDL-associated PON1 can be successfully transferred to cultured cells in vitro and deliver protection from oxidative stress and bacterial substrate of PON1 N-3-oxo-dodecanoyl-L-Homoserine lactone. [40] Beside HDL, some amount of PON1 in human plasma is associated with VLDL and chylomicrons. [41]
While liver is the major tissue of PON1 gene expression, lipoprotein-assisted circulation of PON1 in plasma delivers the enzyme to multiple tissues that do not express PON1 themselves. Immunohistochemical staining of rat tissues revealed PON1 presence in liver, kidney, in endothelial lining of lung and brain. [42] More recent study with mouse tissue detected PON1 protein in hepatocytes, adipocytes, chondrocytes, skeletal and cardiac muscle, kidney, spermatozoa, and epithelial cells of skin, stomach, intestine, trachea, bronchiole, and eye lens. Studies did not find co-localization of PON1 with ApoA-I protein that might mean local PON1 expression or different sources of ApoA-I, an integral component of HDL. [43]
Immunostaining of healthy human aorta shows a low level and granular distribution of PON1 in smooth muscle cells. Western blot confirmed presence of intact and degraded PON1 in media of healthy aorta. With the development of atherosclerosis, PON1 staining of media increases and becomes homogeneous. Increasing accumulation of PON1 with the progression of the atherosclerosis can be seen in the intimal part of aorta as well. Aorta with advanced atherosclerosis lesions shows massive PON1 accumulation. [44] A more recent study attributed an increased PON1 immunostaining in human atherosclerotic arteries to macrophages accumulated in lesions. [45]
| Atheroprotective Effects of PON1 in Animal Models | | |
High-fat, high-cholesterol (atherogenic) diet leads to fast development of atherosclerosis in C57BL/6J mouse strain with concomitant decrease in liver PON1 expression. At the same time PON1 expression and its protective effects did not decrease in atherosclerosis-resistant strain C3H/HeJ. [46]
The first PON1 knockout mouse data became available in 1998. Macrophages from this mouse did not protect LDL from oxidation by other cells in vitro, and PON1 knockout mice developed atherosclerosis faster than control mice on high fat, high cholesterol diet. [13] To study the effect of PON1 knockout further, this mouse was crossed with ApoE knockout mice to generate PON1-/-, ApoE-/- mouse. The double knockout mice fed with atherogenic diet developed atherosclerosis faster than control. Plasma lipid profile of these double knockout mice was similar to ApoE-/- control animals with slightly decreased level of intermediate density lipoprotein (IDL) and LDL, and increased level of lysophosphatidylcholine and oxidized phospholipids in IDL and LDL. The rates of LDL oxidation and clearance were higher in PON1-/-, ApoE-/- mice than in control mice as was determined by injection of human LDL. Expression of genes responding to increase of OxLDL, such as heme oxygenase-1, peroxisome proliferator-activated receptor gamma, scavenger receptor type A, CD36, and macrosialin, was upregulated in liver of PON1-/-, ApoE-/- mice compared with ApoE-/- mice. [47]
Involvement of PON in inflammation and oxidative stress were detected in vascular wall of PON-/- animals. Adhesion of leukocytes was increased in the knockout mouse as measured by intravital microscopy. Expression of mRNA of essential cell adhesion molecules P-selectin and ICAM1 was upregulated in aortic wall. An increased oxidative status was detected using superoxide-sensitive reagent lucigenin. PON-/- mice have a significantly shorter time of occlusion in carotid thrombosis assay. [48] If a deficiency of PON1 leads to inflammation and oxidative stress, then increases in PON1 function could be beneficial. A transgenic mouse mPON1 was developed in 2001, with 5-fold higher level of mouse PON1 protein and corresponding increase in arylesterase activity. PON1 was associated with HDL, and protected HDL from oxidation by copper ions as it was assessed by lipid hydroperoxide formation assay, and by retaining oxidation-sensitive activity of lecithin:cholesterol acyltransferase (LCAT). [49] A decrease in atherosclerotic lesion size and improved oxidation status of aorta and peritoneal macrophages in PON1 overexpressing transgenic mouse on ApoE-/- background have been compared with ApoE-/- control have been reported. [14] In another transgenic mouse model, PON1-Tg, which overexpresses human PON1 gene of 55L/192Q genotype, plasma level of arylesterase activity was twice higher in PON1-Tg mouse compared with control mouse when animals were fed normal chow. The excess of PON1 level resulted in better retaining of its activity after feeding animals with atherogenic diet. PON1 activity decreased to about three-fourth (3/4) of original level after 15 weeks of atherogenic diet feeding to PON1-Tg mice, and to less than one-half (1/2) of original level in control animals. Thus, arylesterase activity mediated by PON1 was almost 4-fold higher in PON1-Tg mice compared with control mice after feeding atherogenic diet. Overexpression of PON1 definitely protected mouse from development of atherosclerotic lesions. Aortic lesion areas in PON1-Tg animals were about half of the size of areas of the control mice after feeding atherogenic diet. ApoE-/-, PON1-Tg genotype mice fed normal chow similarly developed lesions slower, compared with ApoE-/- controls; however, the difference in lesion area was just 22%. Plasma arylesterase activity of ApoE-/-, PON1-Tg mice was 2.5-fold higher than that of ApoE-/- animals, however, there is no difference between their lipid profile. A decreased inflammatory status of aortas in ApoE-/-, PON1-Tg mice compared with ApoE-/- mice was detected by examination of the expression level of MCP-1 cytokine gene. HDL isolated from PON1-Tg mouse plasma or ApoE-/-, PON1-Tg mouse plasma provided better protection against LDL oxidation, than HDL isolated from control animals. [50]
Beside PON1 studies on transgenic mouse, a transient overexpression of PON1 gene in mouse was utilized to investigate effect of PON1. Adenovirus-mediated delivery of human PON1 gene (55M, 192Q genotype) in double knockout leptin-/- (ob/ob), LDLR-/- mouse resulted in more than 4-fold increase of PON1 activity on day 7 with gradual decrease to the control level by day 21. Mice were injected with adenovirus at the age of 18 weeks when the progression of atherosclerosis occurs in a fast rate. Six weeks later, cross-sections of the aortic root were analyzed by immunohistochemistry. Plaque size, volume of macrophages, concentration of OxLDL was significantly lower in PON1 expressing animals. The titer of anti-OxLDL antibodies was lower in plasma of PON1 overexpressing mice as well. [51]
While an early PON1 intervention proved to have significant athero-protective effect, another study was performed to assess whether transient PON1 overexpression can improve vascular function in advanced atherosclerosis. Similar to the previous study, 55M/192Q variant of human PON1 gene was delivered in 18 month old ApoE-/- mouse fed normal chow using adenovirus vector. Serum PON1 activity was increased 10-fold by day 7 and 2.5-fold on the day 21 in PON1 overexpressing animals compared with controls. After 3 weeks, lesions were measured and no changes in their size were found. However, vasomotor function was improved by transient overexpression of PON1. Thus, phenylephrine-constricted segments of the aortas relaxed significantly better in response to endothelium dependent agonists ACh, adenosine-5′-triphosphate (ATP), and uridine-5′-triphosphate (UTP) observations on PON1 role in animal models is summarized in [Table 2]. [52] | Table 2: Summary of observations on alterations of PON1 expression in mice
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| PON1 Serum Activity, Polymorphism and CAD in Human | | |
Meta-analysis of 47 studies with 9853 CAD and 11,408 control subjects published in 2012 confirmed association of lower plasma PON1 activity with increased CAD risk (19% lower PON1 activity, P < 0.00001). [53] Another meta-analysis published in 2012 included 43 studies with total 20,629 subjects showed similar association of PON1 activity and CAD with standardized mean difference (SMD) of -0.78 (P < 0.001) for CAD subjects compared with controls. Slightly weaker association was between arylesterase activity of PON1 and CAD with SMD of -0.50 (P < 0.001). [54] Both meta-analyses observed increased risk of CAD in subjects with lower PON1 regardless of age and ethnicity; [Table 3] and [Table 4] summarizes the role of PON1 in human studies. | Table 3: Summary of allele differences of PON1 in vitro, and conclusions from PON1 human studies
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Some alleles of polymorphous genes can be causative factors in development of diseases and reliable predictors. Several polymorphisms were detected in human PON1 gene. There are at least five known polymorphisms in promoter region of PON1: -909/-907 (C or G), -832/-824 (A or G), -162/-160 (A or G), -126 (C or G), and -108/-107 (C or T). Also, there are two polymorphisms in the PON1 coding region, Q192R (aka rs662 or 575A > G) and L55M (aka rs854560 or 163T > A), and several polymorphisms in 3′ untranslated region of the gene. [62] PON1 protein level in human serum varies more than 13-fold, and variations in the sequence of promoter region of PON1 gene might cause difference in its expression. Two-fold differences in expression level between alleles were observed in cell culture reporter gene assay for three polymorphisms: -909/-907 (C or G), -162/-160 (A or G), and -108/-107 (C or T). Polymorphisms -162/-160 (A or G) is a putative binding site for transcription factor NF-I, and -108/-107 (C or T) is a putative binding site for Sp1. No effect on expression level in the reporter gene assay was observed for -832/-824 (A or G), -162/-160 (A or G) polymorphisms. [18]
Gene expression and enzyme activity studies on PON1 polymorphisms in protein coding region Q192R and L55M resulted in several observations. First, messenger RNA of allele 55M appeared to be more stable than 55L as determined by PCR amplification and restriction analysis of cDNA synthesized from heterozygous liver samples. L55M heterozygous liver had roughly twice more mRNA of 55M allele compared with 55L. That might results in difference in protein expression levels between alleles and ultimately in PON1 activity and protection, although it was not assessed in the study. [63] Q192R and L55M alleles differ in their enzymatic activities. In a study of serum of 279 healthy human subjects hydrolytic activity of PON1 toward paraoxon was depending on both polymorphisms. PON1 protein level was relatively similar for all tested polymorphism variants. Activity of 55M homozygotes were always lower than 55L/M heterozygotes or 55L homozygotes. [64] Later studies revealed that Q192R polymorphism affect PON1 activity toward several substrates. QQ, QR, and RR phenotypes can be reliably determined by assaying PON1 catalytic activities toward two substrates: diazoxon and paraoxon. PON1 of QQ genotype exhibits relatively high activity toward diazoxon and relatively low activity toward paraoxon. RR genotype, opposite to QQ, exhibits low activity toward diazoxon and high activity toward paraoxon. QR phenotype exhibits intermediate activity toward both substrates. [65] 192R PON1 hydrolyzes homocysteine thiolactone faster than 192Q PON1. [66]
Q192R and L55M PON1 enzymes differ in their protection to LDL from oxidation in vitro using LDL oxidation assay with copper in the presence of HDL. PON1 of QQ/MM genotype provides the best antioxidant protection. Protection by PON1 decreases in the order of genotypes QQ > QR > RR with almost no antioxidant activity in RR genotype, and about a half of QQ activity in QR phenotype. The antioxidant activity of PON1 decreased in the series MM > LM > LL, with the activity of LL genotype about a half of activity of MM genotype. [67]
Multiple clinical studies were performed to expose whether PON1 polymorphism may contribute to CAD and other diseases. Currently, analyses of association of PON1 polymorphism with atherosclerosis-related diseases determined just one reliable association, an association of Q192R polymorphism with ischemic stroke. Meta-analysis of 22 studies have been published earlier up to mid of 2009, totaling 7384 ischemic stroke subjects and 11,074 controls revealed odds ratio of 1.10 for G (192R) allele (95% CI: 1.04-1.17). [68] Another meta-analysis study that was published in 2010 and summarized results of 11 studies confirmed that 192R allele confers significant risk of ischemic stroke (odds ratio =1.25, 95% CI: 1.07,1.46, P = 0.006). Surprisingly, this risk is confined to Caucasian subjects, but there is no significant association of 192R allele of PON1 and ischemic stroke in East Asian population. [69]
Association of PON1 polymorphism Q192R with CAD was examined in extensive meta-analysis of studies published before 2011. Per-allele odds ratio for CAD for 192R was 1.11 (95% CI: 1.05, 1.17) based on all studies regardless of their size. However, analysis suggested that small studies were less reliable, perhaps because of small studies bias. No significant association of 192R allele with CAD was observed when 10 larger studies with more than 500 cases each were analyzed. [70] Similar conclusions regarding small study bias and the absence of reliable association of Q192R polymorphism with CAD were concluded in two other independent massive meta-analysis studies published in 2004; [71],[72] also, no association was found between CAD and L55M or -108/-107 (C or T) polymorphisms of PON1 gene. Meta-analysis for L55M and -108/-107 (C or T) PON1 polymorphisms determined per-allele odds ratios for CAD as 0.94 (95% CI: 0.88,1.00) for 55M and 1.02 (95% CI: 0.911.15) for -108/-107 C, respectively. No significant association of L55M or -108/-107 (C or T) PON1 polymorphisms with CAD were observed in an earlier meta-analysis study. [72]
No association between L55M (rs854560) polymorphism and ischemic stroke was found in meta-analysis of 16 studies published before mid-2009 totaling 5518 ischemic stroke subjects and 8951 controls. [68] Similarly, a meta-analysis published in 2010 for 10 studies did not find significant association 55L allele with stroke regardless on the stroke type, age of patients, and ethnicity. [69]
Resent human studies generally support the conclusions of meta-analyses [Table 4]. A novel PON1 polymorphism associated with atherosclerosis was recently revealed, SNP rs854563(A/G). [55]
In conclusion, PON1 antioxidant and anti-inflammatory effect is extensively examined in vitro, in cell culture and animal models. Human studies confirm protective role of PON1 in CAD and another atherosclerosis-related disease, ischemic stroke. Although the current knowledge of PON1 provides valuable insights on the function and role of PON1, yet mechanism of PON1 action is still not well investigated. Transient overexpression of PON1 in mouse demonstrated beneficial effects of PON1 beyond its antiatherogenic properties. Further research of PON1 could potentially lead to new clinical strategies in prevention and treatment of cardiovascular diseases.
| References | | |
| 1. | Primo-Parmo SL, Sorenson RC, Teiber JF, La Du BN, The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. Genomics 1996;33:498-507. 
|
| 2. | Harel M, Aharoni A, Gaidukov L, Brumshtein B, Khersonsky O, Meged R, et al. Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol 2004;11:412-9.
[PUBMED] |
| 3. | Draganov DI, Teiber JF, Speelman A, Osawa Y, Sunahara R, La Du BN. Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res 2005;46:1239-47.
[PUBMED] |
| 4. | Khersonsky O, Tawfik DS. Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase. Biochemistry 2005;44:6371-82.
[PUBMED] |
| 5. | Kerkeni M, Addad F, Chauffert M, Chuniaud L, Miled A, Trivin F, et al. Hyperhomocysteinemia, paraoxonase activity and risk of coronary artery disease. Clin Biochem 2006;39:821-5.
[PUBMED] |
| 6. | Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989;320:915-24.
[PUBMED] |
| 7. | Parthasarathy S, Barnett J, Fong LG. High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein. Biochim Biophys Acta 1990;1044:275-83.
[PUBMED] |
| 8. | Mackness MI, Arrol S, Durrington PN. Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein. FEBS Lett 1991;286:152-4.
[PUBMED] |
| 9. | Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La Du BN. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest 1998;101:1581-90.
[PUBMED] |
| 10. | Mackness MI, Arrol S, Abbott C, Durrington PN. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis 1993;104:129-35.
[PUBMED] |
| 11. | Watson DD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, et al. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 1995;96:2882-91.
|
| 12. | Teiber JF, Draganov DI, La Du BN. Purified human serum PON1 does not protect LDL against oxidation in the in vitro assays initiated with copper or AAPH. J Lipid Res 2004;45:2260-8.
[PUBMED] |
| 13. | Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, et al. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 1998;394:284-7.
[PUBMED] |
| 14. | Rozenberg O, Shih DM, Aviram M. Paraoxonase 1 (PON1) attenuates macrophage oxidative status: Studies in PON1 transfected cells and in PON1 transgenic mice. Atherosclerosis 2005;181:9-18.
[PUBMED] |
| 15. | Hassett C, Richter RJ, Humbert R, Chapline C, Crabb JW, Omiecinski CJ, et al. Characterization of cDNA clones encoding rabbit and human serum paraoxonase: The mature protein retains its signal sequence. Biochemistry 1991;30:10141-9.
[PUBMED] |
| 16. | Mackness B, Beltran-Debon R, Aragones G, Joven J, Camps J, Mackness M. Human tissue distribution of paraoxonases 1 and 2 mRNA. IUBMB Life 2010;62:480-2.
|
| 17. | Shamir R, Hartman C, Karry R, Pavlotzky E, Eliakim R, Lachter J, et al. Paraoxonases (PONs) 1, 2, and 3 are expressed in human and mouse gastrointestinal tract and in Caco-2 cell line: Selective secretion of PON1 and PON2. Free Radic Biol Med 2005;39:336-44.
[PUBMED] |
| 18. | Brophy HV, Hastings MD, Clendenning JB, Richter RJ, Jarvik GP, Furlong CE. Polymorphisms in the human paraoxonase (PON1) promoter. Pharmacogenetics 2001;11:77-84.
|
| 19. | Ikeda Y, Suehiro T, Arii K, Kumon Y, Hashimoto K. High glucose induces transactivation of the human paraoxonase 1 gene in hepatocytes. Metabolism 2008;57:1725-32.
[PUBMED] |
| 20. | Osaki F, Ikeda Y, Suehiro T, Ota K, Tsuzura S, Arii K, et al. Roles of Sp1 and protein kinase C in regulation of human serum paraoxonase 1 (PON1) gene transcription in HepG2 cells. Atherosclerosis 2004;176:279-87.
[PUBMED] |
| 21. | Ota K, Suehiro T, Arii K, Ikeda Y, Kumon Y, Osaki F, et al. Effect of pitavastatin on transactivation of human serum paraoxonase 1 gene. Metabolism 2005;54:142-50.
[PUBMED] |
| 22. | Arii K, Suehiro T, Ota K, Ikeda Y, Kumon Y, Osaki F, et al. Pitavastatin induces PON1 expression through p44 / 42 mitogen-activated protein kinase signaling cascade in Huh7 cells. Atherosclerosis 2009;202:439-45.
[PUBMED] |
| 23. | Deakin S, Leviev I, Guernier S, James RW. Simvastatin modulates expression of the PON1 gene and increases serum paraoxonase: A role for sterol regulatory element-binding protein-2. Arterioscler Thromb Vasc Biol 2003;23:2083-9.
[PUBMED] |
| 24. | Gouédard C, Barouki R, Morel Y. Dietary polyphenols increase paraoxonase 1 gene expression by an aryl hydrocarbon receptor-dependent mechanism. Mol Cell Biol 2004;24:5209-22.
|
| 25. | Jaichander P, Selvarajan K, Garelnabi M, Parthasarathy S. Induction of paraoxonase 1 and apolipoprotein A-I gene expression by aspirin. J Lipid Res 2008;49:2142-8.
|
| 26. | Gouédard C, Barouki R, Morel Y. Induction of the paraoxonase-1 gene expression by resveratrol. Arterioscler Thromb Vasc Biol 2004;24:2378-83.
|
| 27. | Cheng CC, Hsueh CM, Liang KW, Ting CT, Wen CL, Hsu SL. Role of JNK and c-Jun signaling pathway in regulation of human serum paraoxonase 1 gene transcription by berberine in human HepG2 cells. Eur J Pharmacol 2011;650:519-25.
|
| 28. | Gutierrez A, Ratliff EP, Andres AM, Huang X, McKeehan WL, Davis RA. Bile acids decrease hepatic paraoxonase 1 expression and plasma high-density lipoprotein levels via FXR-mediated signaling of FGFR4. Arterioscler Thromb Vasc Biol 2006;26:301-6.
|
| 29. | Shih DM, Kast-Woelbern HR, Wong J, Xia YR, Edwards PA, Lusis AJ. A role for FXR and human FGF-19 in the repression of paraoxonase-1 gene expression by bile acids. J Lipid Res 2006;47:384-92.
|
| 30. | Gonzalvo MC, Gil F, Hernandez AF, Rodrigo L, Villanueva E, Pla A. Human liver paraoxonase (PON1): Subcellular distribution and characterization. J Biochem Mol Toxicol 1998;12:61-9.
|
| 31. | Deakin S, Leviev I, Gomaraschi M, Calabresi L, Franceschini G, James RW. Enzymatically active paraoxonase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J Biol Chem 2002;277:4301-8.
|
| 32. | Deakin S, Moren X, James RW. Very low density lipoproteins provide a vector for secretion of paraoxonase-1 from cells. Atherosclerosis 2005;179:17-25.
|
| 33. | Sorenson RC, Bisgaier CL, Aviram M, Hsu C, Billecke S, La Du BN. Human serum Paraoxonase/Arylesterase's retained hydrophobic N-terminal leader sequence associates with HDLs by binding phospholipids: Apolipoprotein A-I stabilizes activity. Arterioscler Thromb Vasc Biol 1999;19:2214-25.
|
| 34. | Schultz JR, Verstuyft JG, Gong EL, Nichols AV, Rubin EM. Protein composition determines the anti-atherogenic properties of HDL in transgenic mice. Nature 1993;365:762-4.
|
| 35. | Gaidukov L, Tawfik DS. High affinity, stability, and lactonase activity of serum paraoxonase PON1 anchored on HDL with ApoA-I. Biochemistry 2005;44:11843-54.
|
| 36. | Gaidukov L, Viji RI, Yacobson S, Rosenblat M, Aviram M, Tawfik DS. ApoE induces serum paraoxonase PON1 activity and stability similar to ApoA-I. Biochemistry 2010;49:532-8.
|
| 37. | Noto H, Hashimoto Y, Satoh H, Hara M, Iso-o N, Togo M, et al. Exclusive association of paraoxonase 1 with high-density lipoprotein particles in apolipoprotein A-I deficiency. Biochem Biophys Res Commun 2001;289:395-401.
|
| 38. | Ribas V, Sánchez-Quesada JL, Antón R, Camacho M, Julve J, Escolà-Gil JC, et al. Human apolipoprotein A-II enrichment displaces paraoxonase from HDL and impairs its antioxidant properties: A new mechanism linking HDL protein composition and antiatherogenic potential. Circ Res 2004;95:789-97.
|
| 39. | Escolà-Gil JC, Marzal-Casacuberta A, Julve-Gil J, Ishida BY, Ordóñez-Llanos J, Chan L, et al. Human apolipoprotein A-II is a pro-atherogenic molecule when it is expressed in transgenic mice at a level similar to that in humans: Evidence of a potentially relevant species-specific interaction with diet. J Lipid Res 1998;39:457-62.
|
| 40. | Deakin SP, Bioletto S, Bochaton-Piallat ML, James RW. HDL-associated paraoxonase-1 can redistribute to cell membranes and influence sensitivity to oxidative stress. Free Radic Biol Med 2011;50:102-9.
|
| 41. | Fuhrman B, Volkova N, Aviram M. Paraoxonase 1 (PON1) is present in postprandial chylomicrons. Atherosclerosis 2005;180:55-61.
|
| 42. | Rodrigo L, Hernández AF, López-Caballero JJ, Gil F, Pla A. Immunohistochemical evidence for the expression and induction of paraoxonase in rat liver, kidney, lung and brain tissue. Implications for its physiological role. Chem Biol Interact 2001;137:123-37.
|
| 43. | Marsillach J, Mackness B, Mackness M, Riu F, Beltrán R, Joven J, et al. Immunohistochemical analysis of paraoxonases-1, 2, and 3 expression in normal mouse tissues. Free Radic Biol Med 2008;45:146-57.
|
| 44. | Mackness B, Hunt R, Durrington PN, Mackness MI. Increased immunolocalization of paraoxonase, clusterin, and apolipoprotein A-I in the human artery wall with the progression of atherosclerosis. Arterioscler Thromb Vasc Biol 1997;17:1233-8.
|
| 45. | Marsillach J, Camps J, Beltran-Debón J, Rull A, Aragones G, Maestre-Martínez C, et al. Immunohistochemical analysis of paraoxonases-1 and 3 in human atheromatous plaques. Eur J Clin Invest 2011;41:308-14.
|
| 46. | Shih DM, Gu L, Hama S, Xia YR, Navab M, Fogelman AM, et al. Genetic-dietary regulation of serum paraoxonase expression and its role in atherogenesis in a mouse model. J Clin Invest 1996;97:1630-9.
|
| 47. | Shih DM, Xia YR, Wang XP, Miller E, Castellani LW, Subbanagounder G, et al. Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem 2000;275:17527-35.
|
| 48. | Ng DS, Chu T, Esposito B, Hui P, Connelly PW, Gross PL. Paraoxonase-1 deficiency in mice predisposes to vascular inflammation, oxidative stress, and thrombogenicity in the absence of hyperlipidemia. Cardiovasc Pathol 2008;17:226-32.
|
| 49. | Oda MN, Bielicki JK, Ho TT, Berger T, Rubin EM, Forte TM. Paraoxonase 1 overexpression in mice and its effect on high-density lipoproteins. Biochem Biophys Res Commun 2002;290:921-7.
|
| 50. | Tward A, Xia YR, Wang XP, Shi YS, Park C, Castellani LW, et al. Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation 2002;106:484-90.
|
| 51. | Mackness B, Quarck R, Verreth W, Mackness M, Holvoet P. Human paraoxonase-1 overexpression inhibits atherosclerosis in a mouse model of metabolic syndrome. Arterioscler Thromb Vasc Biol 2006;26:1545-50.
|
| 52. | Guns PJ, Van Assche T, Verreth W, Fransen P, Mackness B, Mackness M, et al. Paraoxonase 1 gene transfer lowers vascular oxidative stress and improves vasomotor function in apolipoprotein E-deficient mice with pre-existing atherosclerosis. Br J Pharmacol 2008;153:508-16.
|
| 53. | Wang M, Lang X, Cui S, Zou L, Cao J, Wang S, et al. Quantitative Assessment of the Influence of Paraoxonase 1 Activity and Coronary Heart Disease Risk. DNA Cell Biol 2012;31:975-82.
|
| 54. | Zhao Y, Ma Y, Fang Y, Liu L, Wu S, Fu D, et al. Association between PON1 activity and coronary heart disease risk: A meta-analysis based on 43 studies. Mol Genet Metab 2012;105:141-8.
|
| 55. | Wang Y, Fu W, Xie F, Wang Y, Chu X, Wang H, et al. Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population. J Hum Genet 2010;55:490-4.
|
| 56. | Gungor O, Kircelli F, Demirci MS, Tuncel P, Sisman AR, Tatar E, et al. Serum paraoxonase 1 activity predicts arterial stiffness in renal transplant recipients. J Atheroscler Thromb 2011;18:901-5.
|
| 57. | Gupta N, Singh S, Maturu VN, Sharma YP, Gill KD. Paraoxonase 1 (PON1) polymorphisms, haplotypes and activity in predicting cad risk in North-West Indian Punjabis. PLoS One 2011;6:e17805.
|
| 58. | Gupta N, Binukumar BK, Singh S, Sunkaria A, Kandimalla R, Bhansali A, et al. Serum paraoxonase-1 (PON1) activities (PONase/AREase) and polymorphisms in patients with type 2 diabetes mellitus in a North-West Indian population. Gene 2011;487:88-95.
|
| 59. | Coombes RH, CrowJA, Dail MB, Chambers HW, Wills RW, Bertolet BD, et al. Relationship of human paraoxonase-1 serum activity and genotype with atherosclerosis in individuals from the Deep South. Pharmacogenet Genomics 2011;21:867-75.
|
| 60. | Likidlilid A, Akrawinthawong K, Poldee S, Sriratanasathavorn C. Paraoxonase 1 polymorphisms as the risk factor of coronary heart disease in a Thai population. Acta Cardiol 2010;65:681-91.
|
| 61. | Lüersen K, Schmelzer C, Boesch-Saadatmandi C, Kohl C, Rimbach G, Döring F. Paraoxonase 1 polymorphism Q192R affects the pro-inflammatory cytokine TNF-alpha in healthy males. BMC Res Notes 2011;4:141.
|
| 62. | Brophy VH, Jampsa RL, Clendenning JB, McKinstry LA, Jarvik GP, Furlong CE. Effects of 5' regulatory-region polymorphisms on paraoxonase-gene (PON1) expression. Am J Hum Genet 2001;68:1428-36.
|
| 63. | Leviev I, Negro F, James RW. Two alleles of the human paraoxonase gene produce different amounts of mRNA. An explanation for differences in serum concentrations of paraoxonase associated with the (Leu-Met54) polymorphism. Arterioscler Thromb Vasc Biol 1997;17:2935-9.
|
| 64. | Mackness B, Mackness MI, Arrol S, Turkie W, Durrington PN. Effect of the molecular polymorphisms of human paraoxonase (PON1) on the rate of hydrolysis of paraoxon. Br J Pharmacol 1997;122:265-8.
|
| 65. | Richter RJ, Jampsa RL, Jarvik GP, Costa LG, Furlong CE. Determination of paraoxonase 1 status and genotypes at specific polymorphic sites. Curr Protoc Toxicol 2004; Chapter 4:Unit 4.12.
|
| 66. | Bayrak A, Bayrak T, Demirpençe E, Kýlýnç K. Differential hydrolysis of homocysteine thiolactone by purified human serum (192)Q and (192)R PON1 isoenzymes. J Chromatogr B Analyt Technol Biomed Life Sci 2011;879:49-55.
|
| 67. | Mackness B, Mackness MI, Arrol S, Turkie W, Durrington PN. Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification. FEBS Lett 1998;423:57-60.
|
| 68. | Dahabreh IJ, Kitsios GD, Kent DM, Trikalinos TA. Paraoxonase 1 polymorphisms and ischemic stroke risk: A systematic review and meta-analysis. Genet Med 2010;12:606-15.
|
| 69. | Banerjee I. Relationship between Paraoxonase 1 (PON1) gene polymorphisms and susceptibility of stroke: A meta-analysis. Eur J Epidemiol 2010;25:449-58.
|
| 70. | Wang M, Lang X, Zou L, Huang S, Xu Z. Four genetic polymorphisms of paraoxonase gene and risk of coronary heart disease: A meta-analysis based on 88 case-control studies. Atherosclerosis 2011;214:377-85.
|
| 71. | Lawlor DA, Day IN, Gaunt TR, Hinks LJ, Briggs PJ, Kiessling M, et al. The association of the PON1 Q192R polymorphism with coronary heart disease: Findings from the British Women's Heart and Health cohort study and a meta-analysis. BMC Genet 2004;5:17.
|
| 72. | Wheeler JG, Keavney BD, Watkins H, Collins R, Danesh J. Four paraoxonase gene polymorphisms in 11212 cases of coronary heart disease and 12786 controls: Meta-analysis of 43 studies. Lancet 2004;363:689-95.
|
[Figure 1]
[Table 1], [Table 2], [Table 3], [Table 4]
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Oxidative Stress in the Pathogenesis of Antiphospholipid Syndrome: Implications for the Atherothrombotic Process |
|
| Cristina Nocella, Simona Bartimoccia, Vittoria Cammisotto, Alessandra D’Amico, Daniele Pastori, Giacomo Frati, Sebastiano Sciarretta, Paolo Rosa, Chiara Felici, Oliviero Riggio, Antonella Calogero, Roberto Carnevale | | Antioxidants. 2021; 10(11): 1790 | | [Pubmed] | [DOI] | | | 42 |
Obesity Affects HDL Metabolism, Composition and Subclass Distribution |
|
| Julia T. Stadler,Sonja Lackner,Sabrina Mörkl,Athina Trakaki,Hubert Scharnagl,Andrea Borenich,Willibald Wonisch,Harald Mangge,Sieglinde Zelzer,Nathalie Meier-Allard,Sandra J. Holasek,Gunther Marsche | | Biomedicines. 2021; 9(3): 242 | | [Pubmed] | [DOI] | | | 43 |
Fetal High-Density Lipoproteins: Current Knowledge on Particle Metabolism, Composition and Function in Health and Disease |
|
| Julia T. Stadler,Christian Wadsack,Gunther Marsche | | Biomedicines. 2021; 9(4): 349 | | [Pubmed] | [DOI] | | | 44 |
Genetic Regulation of Biomarkers as Stress Proxies in Dairy Cows |
|
| Marco Milanesi,Matilde Maria Passamonti,Katia Cappelli,Andrea Minuti,Valentino Palombo,Sandy Sgorlon,Stefano Capomaccio,Mariasilvia D’Andrea,Erminio Trevisi,Bruno Stefanon,John Lewis Williams,Paolo Ajmone-Marsan | | Genes. 2021; 12(4): 534 | | [Pubmed] | [DOI] | | | 45 |
Effects of Moringa oleifera Leaf Extract on Diabetes-Induced Alterations in Paraoxonase 1 and Catalase in Rats Analyzed through Progress Kinetic and Blind Docking |
|
| Erick Sierra-Campos,Mónica Valdez-Solana,Claudia Avitia-Domínguez,Mara Campos-Almazán,Ismael Flores-Molina,Guadalupe García-Arenas,Alfredo Téllez-Valencia | | Antioxidants. 2020; 9(9): 840 | | [Pubmed] | [DOI] | | | 46 |
Whole-Body Cryostimulation Improves Inflammatory Endothelium Parameters and Decreases Oxidative Stress in Healthy Subjects |
|
| Agata Stanek,Tomasz Wielkoszynski,Stanislaw Bartus,Armand Cholewka | | Antioxidants. 2020; 9(12): 1308 | | [Pubmed] | [DOI] | | | 47 |
Obesity-Related Changes in High-Density Lipoprotein Metabolism and Function |
|
| Julia T. Stadler,Gunther Marsche | | International Journal of Molecular Sciences. 2020; 21(23): 8985 | | [Pubmed] | [DOI] | | | 48 |
Paraoksonaz 1: Çocuklarda astim için önemli olabilir mi? |
|
| I?rfan SAHIN,Osman GÜLSEVER | | Kahramanmaras Sütçü Imam Üniversitesi Tip Fakültesi Dergisi. 2020; | | [Pubmed] | [DOI] | | | 49 |
ApoE-Derived Peptides Attenuated Diabetes-Induced Oxidative Stress and Inflammation |
|
| Sunil A. Nankar,Yogesh Bulani,Shyam S. Sharma,Abhay H. Pande | | Protein & Peptide Letters. 2020; 27(3): 193 | | [Pubmed] | [DOI] | | | 50 |
Polyphenolic Compounds and Gut Microbiome in Cardiovascular Diseases |
|
| Lindsay McGrail,Mahdi Garelnabi | | Current Pharmaceutical Biotechnology. 2020; 21(7): 578 | | [Pubmed] | [DOI] | | | 51 |
p-Cymene Modulate Oxidative Stress and Inflammation in Murine Macrophages: Potential Implication in Atherosclerosis |
|
| Tong Wu,Zahra Mazhar,Dhuha Alsayrafi,Mahdi Garelnabi | | Cardiovascular & Hematological Agents in Medicinal Chemistry. 2020; 18(2): 151 | | [Pubmed] | [DOI] | | | 52 |
African Walnuts (Tetracarpidium conophorum) Modulate Hepatic Lipid Accumulation in Obesity via Reciprocal Actions on HMG-CoA Reductase and Paraoxonase |
|
| Daniel E. Uti,Item J. Atangwho,Eyong U. Eyong,Grace U. Umoru,Godwin E. Egbung,Solomon O. Rotimi,Victor U. Nna | | Endocrine, Metabolic & Immune Disorders - Drug Targets. 2020; 20(3): 365 | | [Pubmed] | [DOI] | | | 53 |
Effects of disease activity on lipoprotein levels in patients with early arthritis: can oxidized LDL cholesterol explain the lipid paradox theory? |
|
| Ana M. Fernández-Ortiz,Ana M. Ortiz,Silvia Pérez,Esther Toledano,Lydia Abásolo,Miguel A. González-Gay,Santos Castańeda,Isidoro González-Álvaro | | Arthritis Research & Therapy. 2020; 22(1) | | [Pubmed] | [DOI] | | | 54 |
Curcumin exerts hepatoprotection via overexpression of Paraoxonase-1 and its regulatory genes in rats undergone bile duct ligation |
|
| Ameneh Khodarahmi,Davoud Javidmehr,Azam Eshaghian,Zohreh-al-sadat Ghoreshi,Alireza Karimollah,Hamidreza Yousefi,Ali Moradi | | Journal of Basic and Clinical Physiology and Pharmacology. 2020; 0(0) | | [Pubmed] | [DOI] | | | 55 |
Nutrition, Thrombosis, and Cardiovascular Disease |
|
| Francesco Violi,Daniele Pastori,Pasquale Pignatelli,Roberto Carnevale | | Circulation Research. 2020; 126(10): 1415 | | [Pubmed] | [DOI] | | | 56 |
Amelioration of cyclosporine-induced testicular toxicity by carvedilol and/or alpha-lipoic acid: Role of TGF-ß1, the proinflammatory cytokines, Nrf2/HO-1 pathway and apoptosis |
|
| Ahmed M. Kabel,Samir A. Salama,Amal A. Alghorabi,Remon S. Estfanous | | Clinical and Experimental Pharmacology and Physiology. 2020; | | [Pubmed] | [DOI] | | | 57 |
Diving deep: understanding the genetic components of hypoxia tolerance in marine mammals |
|
| Allyson G. Hindle | | Journal of Applied Physiology. 2020; 128(5): 1439 | | [Pubmed] | [DOI] | | | 58 |
Genetic Variability of Antioxidative Mechanisms and Cardiotoxicity after Adjuvant Radiotherapy in HER2-Positive Breast Cancer Patients |
|
| Tanja Marinko,Jakob Timotej Stojanov Konda,Vita Dolžan,Katja Goricar,Anca Daniela Farcas | | Disease Markers. 2020; 2020: 1 | | [Pubmed] | [DOI] | | | 59 |
Association of Race and Major Adverse Cardiac Events (MACE): The Atherosclerosis Risk in Communities (ARIC) Cohort |
|
| Ericha G Franey,Donna Kritz-Silverstein,Erin L Richard,John E Alcaraz,Caroline M Nievergelt,Richard A Shaffer,Vibha Bhatnagar | | Journal of Aging Research. 2020; 2020: 1 | | [Pubmed] | [DOI] | | | 60 |
Modulation of oxidative stress/antioxidative defence in human serum treated by four different tyrosine kinase inhibitors |
|
| Marija Mihajlovic,Branka Ivkovic,Biljana Jancic-Stojanovic,Aleksandra Zeljkovic,Vesna Spasojevic-Kalimanovska,Jelena Kotur-Stevuljevic,Dragana Vujanovic | | Anti-Cancer Drugs. 2020; 31(9): 942 | | [Pubmed] | [DOI] | | | 61 |
Betanin as a multipath oxidative stress and inflammation modulator: a beetroot pigment with protective effects on cardiovascular disease pathogenesis |
|
| Davi Vieira Teixeira da Silva,Diego dos Santos Baiăo,Vitor Francisco Ferreira,Vania Margaret Flosi Paschoalin | | Critical Reviews in Food Science and Nutrition. 2020; : 1 | | [Pubmed] | [DOI] | | | 62 |
Effect of acyl and alkyl analogs of platelet-activating factor on inflammatory signaling |
|
| Gopal Kedihithlu Marathe,Vyala Hanumanthareddy Chaithra,Liang-Yin Ke,Chu-Huang Chen | | Prostaglandins & Other Lipid Mediators. 2020; 151: 106478 | | [Pubmed] | [DOI] | | | 63 |
Phytochemicals and endothelial dysfunction: recent advances and perspectives |
|
| Alexandra Bujor,Anca Miron,Adriana Trifan,Simon Vlad Luca,Elvira Gille,Sorin-Dan Miron,Ana Clara Aprotosoaie | | Phytochemistry Reviews. 2020; | | [Pubmed] | [DOI] | | | 64 |
Changes in extrapulmonary organs and serum enzyme biomarkers after chronic exposure to Buenos Aires air pollution |
|
| Guillermo Alberto Maglione,Melisa Lidia Kurtz,Nadia Soledad Orona,Francisco Astort,Fernando Brites,Celina Morales,Alejandro Berra,Deborah Ruth Tasat | | Environmental Science and Pollution Research. 2020; | | [Pubmed] | [DOI] | | | 65 |
PON-1 haplotype (-108C>T, L55M, and Q192R) modulates the serum levels and activity PONase promoting an atherogenic lipid profile in rheumatoid arthritis patients |
|
| Oscar Zaragoza-García,Iris Paola Guzmán-Guzmán,Ma. Elena Moreno-Godínez,José Eduardo Navarro-Zarza,Verónica Antonio-Vejar,Mónica Ramírez,Isela Parra-Rojas | | Clinical Rheumatology. 2020; | | [Pubmed] | [DOI] | | | 66 |
Association between serum paraoxonase 1 activity and its polymorphisms with multiple sclerosis: a systematic review |
|
| Nader Salari,Shna Rasoulpoor,Amin Hosseinian-Far,Nazanin Razazian,Kamran Mansouri,Masoud Mohammadi,Aliakbar Vaisi-Raygani,Rostam Jalali,Shervin Shabani | | Neurological Sciences. 2020; | | [Pubmed] | [DOI] | | | 67 |
Towards treatment planning of COVID-19: Rationale and hypothesis for the use of multiple immunosuppressive agents: Anti-antibodies, immunoglobulins, and corticosteroids |
|
| Amene Saghazadeh,Nima Rezaei | | International Immunopharmacology. 2020; 84: 106560 | | [Pubmed] | [DOI] | | | 68 |
Polycystic ovary syndrome and endothelial dysfunction: A potential role for soluble lectin-like oxidized low density lipoprotein receptor-1 |
|
| Mahmut Oncul,Mustafa Albayrak,Volkan Sozer,Burcin Karakus,Remise Gelisgen,Suat Karatas,Gonul Simsek,Hafize Uzun | | Reproductive Biology. 2020; | | [Pubmed] | [DOI] | | | 69 |
Immature surfactant protein-B impairs the antioxidant capacity of HDL |
|
| Cristina Banfi,Maura Brioschi,Minna K. Karjalainen,Johanna M. Huusko,Erica Gianazza,Piergiuseppe Agostoni | | International Journal of Cardiology. 2019; | | [Pubmed] | [DOI] | | | 70 |
Intravenous laser wavelength radiation effect on LCAT, PON1, catalase, and FRAP in diabetic rats |
|
| Ahmad Amjadi,Hossein Mirmiranpour,Seyed Omid Sobhani,Niloofar Moazami Goudarzi | | Lasers in Medical Science. 2019; | | [Pubmed] | [DOI] | | | 71 |
Paraoxonase Activity in Patients with Obstructive Sleep Apnea: a Systematic Review and Meta-analysis |
|
| Reza Fadaei,Roya Safari-Faramani,Mohammad Rezaei,Reza Ahmadi,Masoumeh Rostampour,Nariman Moradi,Habibolah Khazaie | | SN Comprehensive Clinical Medicine. 2019; | | [Pubmed] | [DOI] | | | 72 |
Activity of Lipoprotein-Associated Enzymes in Argentinean Indigenous Children Living at Different Altitudes |
|
| Valeria Hirschler,Maximiliano Martin,Claudia Molinari,Eliana Botta,Walter Francisco Tetzlaff,Fernando Brites | | Archives of Medical Research. 2019; 50(3): 98 | | [Pubmed] | [DOI] | | | 73 |
Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites |
|
| J. Nie,L. Zhang,G. Zhao,X. Du | | Journal of Applied Microbiology. 2019; | | [Pubmed] | [DOI] | | | 74 |
Circulating Lactonase Activity but Not Protein Level of PON-1 Predicts Adverse Outcomes in Subjects with Chronic Kidney Disease |
|
| Chrysan J. Mohammed,Yanmei Xie,Pamela S. Brewster,Subhanwita Ghosh,Prabhatchandra Dube,Tiana Sarsour,Andrew L. Kleinhenz,Erin L. Crawford,Deepak Malhotra,Richard W. James,Philip A. Kalra,Steven T. Haller,David J. Kennedy | | Journal of Clinical Medicine. 2019; 8(7): 1034 | | [Pubmed] | [DOI] | | | 75 |
Cynanchum wilfordii Etanolic Extract Controls Blood Cholesterol: A Double-blind, Randomized, Placebo-Controlled, Parallel Trial |
|
| Taghi Youn,Taghi Ham,Taghi Yoon,Taghi Choi,Taghi Lee,Taghi Cho,Taghi Kim | | Nutrients. 2019; 11(4): 836 | | [Pubmed] | [DOI] | | | 76 |
Cardiotoxicity and lung toxicity in male rats induced by long-term exposure to iron oxide and silver nanoparticles |
|
| Mokhtar Yousef,Abdelsalam Abuzreda,Maher Kamel | | Experimental and Therapeutic Medicine. 2019; | | [Pubmed] | [DOI] | | | 77 |
Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians |
|
| Sumanpreet Kaur, Gurjit Kaur Bhatti, Rajesh Vijayvergiya, Puneetpal Singh, Sarabjit Singh Mastana, Rupinder Tewari, Jasvinder Singh Bhatti | | International Journal of Diabetes and Metabolism. 2018; : 38 | | [Pubmed] | [DOI] | | | 78 |
Association Between Oxidation-Modified Lipoproteins and Coronary Plaque in Psoriasis |
|
| Alexander V. Sorokin,Kazuhiko Kotani,Youssef A. Elnabawi,Amit K. Dey,Aparna P. Sajja,Shingo Yamada,Masashi Ueda,Charlotte L. Harrington,Yvonne Baumer,Justin A. Rodante,Joel M. Gelfand,Marcus Y. Chen,Aditya A. Joshi,Martin P. Playford,Alan T. Remaley,Nehal N. Mehta | | Circulation Research. 2018; 123(11): 1244 | | [Pubmed] | [DOI] | | | 79 |
HDL in CKD—The Devil Is in the Detail |
|
| Florian Kronenberg | | Journal of the American Society of Nephrology. 2018; 29(5): 1356 | | [Pubmed] | [DOI] | | | 80 |
Carotid Artery Atherosclerosis: A Review on Heritability and Genetics |
|
| Bianka Forgo,Emanuela Medda,Anita Hernyes,Laszlo Szalontai,David Laszlo Tarnoki,Adam Domonkos Tarnoki | | Twin Research and Human Genetics. 2018; : 1 | | [Pubmed] | [DOI] | | | 81 |
Association of carotid intima media thickness with atherogenic index of plasma, apo B/apo A-I ratio and paraoxonase activity in patients with non-alcoholic fatty liver disease |
|
| Reza Fadaei,Reza Meshkani,Hossein Poustchi,Soudabeh Fallah,Nariman Moradi,Ghodratollah Panahi,Shahin Merat,Taghi Golmohammadi | | Archives of Physiology and Biochemistry. 2018; : 1 | | [Pubmed] | [DOI] | | | 82 |
Some indazoles reduced the activity of human serum paraoxonase 1, an antioxidant enzyme: in vitro inhibition and molecular modeling studies |
|
| Zuhal Alim,Deryanur Kiliç,Yeliz Demir | | Archives of Physiology and Biochemistry. 2018; : 1 | | [Pubmed] | [DOI] | | | 83 |
Incorporation of whole oat, especially bran, into a high-fat diet, improves cardio-metabolic risk factors in type 2 diabetic rats |
|
| Fatima Bensalah,Nour el Imane Harrat,Fouad Affane,Hadjera Chekkal,Myriem Lamri-Senhadji | | Nutrition & Food Science. 2018; | | [Pubmed] | [DOI] | | | 84 |
High-density lipoprotein mimetic nanotherapeutics for cardiovascular and neurodegenerative diseases |
|
| Song Ih Ahn,Hyun-Ji Park,Jiwon Yom,Taeyoung Kim,YongTae Kim | | Nano Research. 2018; | | [Pubmed] | [DOI] | | | 85 |
Association of paraoxonase-1 gene polymorphisms with insulin resistance in South Indian population |
|
| Panneerselvam Gomathi,Anandi Chandramouli Iyer,Ponniah Senthil Murugan,Sundaresan Sasikumar,Nancy Bright Arul Joseph Raj,Divya Ganesan,Sivagnanam Nallaperumal,Maruthamuthu Murugan,Govindan Sadasivam Selvam | | Gene. 2018; | | [Pubmed] | [DOI] | | | 86 |
Autophagy Ablation in Adipocytes Induces Insulin Resistance and Reveals Roles for Lipid Peroxide and Nrf2 Signaling in Adipose-Liver Crosstalk |
|
| Jinjin Cai,Karla M. Pires,Maroua Ferhat,Bhagirath Chaurasia,Márcio A. Buffolo,Rana Smalling,Ashot Sargsyan,Donald L. Atkinson,Scott A. Summers,Timothy E. Graham,Sihem Boudina | | Cell Reports. 2018; 25(7): 1708 | | [Pubmed] | [DOI] | | | 87 |
A case control study on HDL associated PON1 enzyme level in Northern Indian type 2 diabetes mellitus patients |
|
| Mohd Wamique,Wahid Ali,D. Himanshu Reddy,Preeti Vishwakarma,Mohd Waseem | | Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2018; | | [Pubmed] | [DOI] | | | 88 |
Strategies in the designing of prodrugs, taking into account the antiviral and anticancer compounds |
|
| Monika A. Lesniewska-Kowiel,Izabela Muszalska | | European Journal of Medicinal Chemistry. 2017; 129: 53 | | [Pubmed] | [DOI] | | | 89 |
Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis |
|
| Robert Wolk,Ehrin J. Armstrong,Peter R. Hansen,Bruce Thiers,Shuping Lan,Anna M. Tallman,Mandeep Kaur,Svitlana Tatulych | | Journal of Clinical Lipidology. 2017; | | [Pubmed] | [DOI] | | | 90 |
Role of polyphenols and polyphenol-rich foods in the modulation of PON1 activity and expression |
|
| Daniela Martini,Cristian Del Bo’,Marisa Porrini,Salvatore Ciappellano,Patrizia Riso | | The Journal of Nutritional Biochemistry. 2017; 48: 1 | | [Pubmed] | [DOI] | | | 91 |
Phenol-enriched olive oils modify paraoxonase-related variables: A randomized, crossover, controlled trial |
|
| Sara Fernández-Castillejo,Ana-Isabel García-Heredia,Rosa Solŕ,Jordi Camps,Maria-Carmen López de la Hazas,Marta Farrŕs,Anna Pedret,Úrsula Catalán,Laura Rubió,Maria-José Motilva,Olga Castańer,María-Isabel Covas,Rosa-Maria Valls | | Molecular Nutrition & Food Research. 2017; : 1600932 | | [Pubmed] | [DOI] | | | 92 |
Dietary polyphenols for atherosclerosis: A comprehensive review and future perspectives |
|
| Roodabeh Bahramsoltani,Farnaz Ebrahimi,Mohammad Hosein Farzaei,Armaghan Baratpourmoghaddam,Pardis Ahmadi Borkani,Pourouchista Rostamiasrabadi,Amir Hosein Rasouli Amirabadi,Roja Rahimi | | Critical Reviews in Food Science and Nutrition. 2017; : 00 | | [Pubmed] | [DOI] | | | 93 |
Apolipoprotein L1 and apolipoprotein A-IV and their association with kidney function |
|
| Florian Kronenberg | | Current Opinion in Lipidology. 2017; 28(1): 39 | | [Pubmed] | [DOI] | | | 94 |
Cholesterol reduction and macrophage function |
|
| C. Roger White,G.M. Anantharamaiah | | Current Opinion in Lipidology. 2017; 28(5): 397 | | [Pubmed] | [DOI] | | | 95 |
Type 2 Diabetes in Young Females Results in Increased Serum Amyloid A and Changes to Features of High Density Lipoproteins in Both HDL2 and HDL3 |
|
| Kayleigh Griffiths,Agnieszka Pazderska,Mohammed Ahmed,Anne McGowan,Alexander P. Maxwell,Jane McEneny,James Gibney,Gareth J. McKay | | Journal of Diabetes Research. 2017; 2017: 1 | | [Pubmed] | [DOI] | | | 96 |
Bis(4,4'-dimethyl-2,2'-bipyridine)oxidovanadium(IV) Sulfate Dehydrate: Potential Candidate for Controlling Lipid Metabolism? |
|
| Renata Francik,Jadwiga Kryczyk-Koziol,Slawomir Francik,Ryszard Grybos,Miroslaw Krosniak | | BioMed Research International. 2017; 2017: 1 | | [Pubmed] | [DOI] | | | 97 |
Effects of Vitamin C on Paraoxonase1 Arylesterase Activity in Rats Exposed to Arsenic |
|
| Felor Zargari,Hamid Tabaghchi Saeedy | | Iranian Jornal of Toxicology. 2017; 11(3): 47 | | [Pubmed] | [DOI] | | | 98 |
Effect of rosuvastatin on fasting and postprandial endothelial biomarker levels and microvascular reactivity in patients with type 2 diabetes and dyslipidemia: a preliminary report |
|
| Kyoung Min Kim,Kyong Yeun Jung,Han Mi Yun,Seo Young Lee,Tae Jung Oh,Hak Chul Jang,Soo Lim | | Cardiovascular Diabetology. 2017; 16(1) | | [Pubmed] | [DOI] | | | 99 |
The Role of Omega-3 Fatty Acids in Reverse Cholesterol Transport: A Review |
|
| Alex Pizzini,Lukas Lunger,Egon Demetz,Richard Hilbe,Guenter Weiss,Christoph Ebenbichler,Ivan Tancevski | | Nutrients. 2017; 9(10): 1099 | | [Pubmed] | [DOI] | | | 100 |
Combined Effects of Curcumin and Lycopene or Bixin in Yoghurt on Inhibition of LDL Oxidation and Increases in HDL and Paraoxonase Levels in Streptozotocin-Diabetic Rats |
|
| Renata Assis,Carlos Arcaro,Vânia Gutierres,Juliana Oliveira,Paulo Costa,Amanda Baviera,Iguatemy Brunetti | | International Journal of Molecular Sciences. 2017; 18(4): 332 | | [Pubmed] | [DOI] | | | 101 |
Isoliquiritigenin Attenuates Atherogenesis in Apolipoprotein E-Deficient Mice |
|
| Fen Du,Quzhen Gesang,Jia Cao,Mei Qian,Li Ma,Dongfang Wu,Hong Yu | | International Journal of Molecular Sciences. 2016; 17(11): 1932 | | [Pubmed] | [DOI] | | | 102 |
Modified Lipids and Lipoproteins in Chronic Kidney Disease: A New Class of Uremic Toxins |
|
| Nans Florens,Catherine Calzada,Egor Lyasko,Laurent Juillard,Christophe Soulage | | Toxins. 2016; 8(12): 376 | | [Pubmed] | [DOI] | | | 103 |
Serum paraoxonase-1 gene polymorphism and enzyme activity in patients with urolithiasis |
|
| Arda Atar,Asuman Gedikbasi,Erkan Sonmezay,Zeynep Kusku Kiraz,Semra Abbasoglu,Ali Ihsan Tasci,Volkan Tugcu | | Renal Failure. 2016; 38(3): 378 | | [Pubmed] | [DOI] | | | 104 |
PON-1 Activity and Plasma 8-Isoprostane Concentration in Patients with Angiographically Proven Coronary Artery Disease |
|
| Agnieszka Kuchta,Adrian Strzelecki,Agnieszka Cwiklinska,Magdalena Toton,Marcin Gruchala,Zbigniew Zdrojewski,Barbara Kortas-Stempak,Anna Gliwinska,Kamil Dabkowski,Maciej Jankowski | | Oxidative Medicine and Cellular Longevity. 2016; 2016: 1 | | [Pubmed] | [DOI] | | | 105 |
Açai (Euterpe oleraceaMart.) Upregulates Paraoxonase 1 Gene Expression and Activity with Concomitant Reduction of Hepatic Steatosis in High-Fat Diet-Fed Rats |
|
| Renata Rebeca Pereira,Isabel Cristina Mallosto Emerich de Abreu,Joyce Ferreira da Costa Guerra,Nara Nunes Lage,Juliana Márcia Macedo Lopes,Maísa Silva,Wanderson Geraldo de Lima,Marcelo Eustáquio Silva,Maria Lucia Pedrosa | | Oxidative Medicine and Cellular Longevity. 2016; 2016: 1 | | [Pubmed] | [DOI] | | | 106 |
Diosmin attenuates radiation-induced hepatic fibrosis by boosting PPAR-? expression and hampering miR-17-5p-activated canonical Wnt–ß-catenin signaling |
|
| Hesham Farouk Hasan,Mohamed Khairy Abdel-Rafei,Shereen Mohamed Galal | | Biochemistry and Cell Biology. 2016; : 1 | | [Pubmed] | [DOI] | | | 107 |
Strawberries Added to the Usual Diet Suppress Fasting Plasma Paraoxonase Activity and Have a Weak Transient Decreasing Effect on Cholesterol Levels in Healthy Nonobese Subjects |
|
| Anna Zasowska-Nowak,Piotr J. Nowak,Piotr Bialasiewicz,Anna Prymont-Przyminska,Anna Zwolinska,Agata Sarniak,Anna Wlodarczyk,Jaroslaw Markowski,Krzysztof P. Rutkowski,Dariusz Nowak | | Journal of the American College of Nutrition. 2016; : 1 | | [Pubmed] | [DOI] | | | 108 |
The Effects of Ellagic Acid upon Brain Cells: A Mechanistic View and Future Directions |
|
| Marcos Roberto de Oliveira | | Neurochemical Research. 2016; | | [Pubmed] | [DOI] | | | 109 |
The effect of HDL-bound and free PON1 on copper-induced LDL oxidation |
|
| Ahmet Bayrak,Tülin Bayrak,Ebru Bodur,Kamer Kilinç,Ediz Demirpençe | | Chemico-Biological Interactions. 2016; 257: 141 | | [Pubmed] | [DOI] | | | 110 |
Organophosphate-degrading metallohydrolases: Structure and function of potent catalysts for applications in bioremediation |
|
| Gerhard Schenk,Irsa Mateen,Tee-Kheang Ng,Marcelo M. Pedroso,Nataša Mitic,Miguel Jafelicci,Rodrigo F.C. Marques,Lawrence R. Gahan,David L. Ollis | | Coordination Chemistry Reviews. 2016; 317: 122 | | [Pubmed] | [DOI] | | | 111 |
APOL1 Kidney Disease Risk Variants: An Evolving Landscape |
|
| Patrick D. Dummer,Sophie Limou,Avi Z. Rosenberg,Jurgen Heymann,George Nelson,Cheryl A. Winkler,Jeffrey B. Kopp | | Seminars in Nephrology. 2015; 35(3): 222 | | [Pubmed] | [DOI] | | | 112 |
Hyperlipidemia-induced hepatic and small intestine ER stress and decreased paraoxonase 1 expression and activity is associated with HDL dysfunction in Syrian hamsters |
|
| Camelia S. Stancu,Mihaela G. Carnuta,Gabriela M. Sanda,Laura Toma,Mariana Deleanu,Loredan S. Niculescu,Shlomo Sasson,Maya Simionescu,Anca V. Sima | | Molecular Nutrition & Food Research. 2015; 59(11): 2293 | | [Pubmed] | [DOI] | | | 113 |
Altered lipid peroxidation markers are related to post-traumatic stress disorder (PTSD) and not trauma itself in earthquake survivors |
|
| Abdullah Atli,Mahmut Bulut,Yasin Bez,Ibrahim Kaplan,Pinar Güzel Özdemir,Cem Uysal,Hilal Selçuk,Aytekin Sir | | European Archives of Psychiatry and Clinical Neuroscience. 2015; | | [Pubmed] | [DOI] | | | 114 |
How HDL protects LDL against atherogenic modification |
|
| Handrean Soran,Jonathan D. Schofield,Yifen Liu,Paul N. Durrington | | Current Opinion in Lipidology. 2015; 26(4): 247 | | [Pubmed] | [DOI] | | | 115 |
The Role of Oxidative Damage in the Pathogenesis and Progression of Alzheimer’s Disease and Vascular Dementia |
|
| Maria Luca,Antonina Luca,Carmela Calandra | | Oxidative Medicine and Cellular Longevity. 2015; 2015: 1 | | [Pubmed] | [DOI] | | | 116 |
The Influence of Urinary Concentrations of Organophosphate Metabolites on the Relationship between BMI and Cardiometabolic Health Risk |
|
| Mahsa Ranjbar,Michael A. Rotondi,Chris I. Ardern,Jennifer L. Kuk | | Journal of Obesity. 2015; 2015: 1 | | [Pubmed] | [DOI] | | | 117 |
Antioxidant properties of HDL |
|
| Handrean Soran,Jonathan D. Schofield,Paul N. Durrington | | Frontiers in Pharmacology. 2015; 6 | | [Pubmed] | [DOI] | | | 118 |
Paraoxonase 1 Activity in Patients with Chronic Obstructive Pulmonary Disease |
|
| Lada Rumora,Marija Grdic Rajkovic,Lara Milevoj Kopcinovic,Dolores Pancirov,Ivana Cepelak,Tihana Žanic Grubišic | | COPD: Journal of Chronic Obstructive Pulmonary Disease. 2014; 11(5): 539 | | [Pubmed] | [DOI] | | | 119 |
Gene-Based Sequencing Identifies Lipid-Influencing Variants with Ethnicity-Specific Effects in African Americans |
|
| Amy R. Bentley,Guanjie Chen,Daniel Shriner,Ayo P. Doumatey,Jie Zhou,Hanxia Huang,James C. Mullikin,Robert W. Blakesley,Nancy F. Hansen,Gerard G. Bouffard,Praveen F. Cherukuri,Baishali Maskeri,Alice C. Young,Adebowale Adeyemo,Charles N. Rotimi,Samuli Ripatti | | PLoS Genetics. 2014; 10(3): e1004190 | | [Pubmed] | [DOI] | | | 120 |
Paraoxonase (PON)1 Q192R functional genotypes and PON1 Q192R genotype by smoking interactions are risk factors for the metabolic syndrome, but not overweight or obesity |
|
| Chiara Cristina Bortolasci,Heber Odebrecht Vargas,André Souza-Nogueira,Estefania Gastaldello Moreira,Sandra Odebrecht Vargas Nunes,Michael Berk,Seetal Dodd,Décio Sabbatini Barbosa,Michael Maes | | Redox Report. 2014; 19(6): 232 | | [Pubmed] | [DOI] | | | 121 |
Quercetin intake with exercise modulates lipoprotein metabolism and reduces atherosclerosis plaque formation |
|
| Mahdi Garelnabi,Halleh Mahini,Thomas Wilson | | Journal of the International Society of Sports Nutrition. 2014; 11(1): 22 | | [Pubmed] | [DOI] | | | 122 |
Association of chemerin with oxidative stress, inflammation and classical adipokines in non-diabetic obese patients |
|
| Péter Fülöp,Ildikó Seres,Hajnalka Lorincz,Mariann Harangi,Sándor Somodi,György Paragh | | Journal of Cellular and Molecular Medicine. 2014; : n/a | | [Pubmed] | [DOI] | | | 123 |
HDL lipid composition is profoundly altered in patients with type 2 diabetes and atherosclerotic vascular disease |
|
| C. Morgantini,D. Meriwether,S. Baldi,E. Venturi,S. Pinnola,A.C. Wagner,A.M. Fogelman,E. Ferrannini,A. Natali,S.T. Reddy | | Nutrition, Metabolism and Cardiovascular Diseases. 2014; | | [Pubmed] | [DOI] | | | 124 |
The platelet activating factor acetyl hydrolase, oxidized low-density lipoprotein, paraoxonase 1 and arylesterase levels in treated and untreated patients with polycystic ovary syndrome |
|
| Ayse Carlioglu,Ikbal Kaygusuz,Feridun Karakurt,Ilknur Inegol Gumus,Aysel Uysal,Benan Kasapoglu,Ferah Armutcu,Sema Uysal,Esra Aktepe Keskin,Cemile Koca | | Archives of Gynecology and Obstetrics. 2014; | | [Pubmed] | [DOI] | | | 125 |
Increased levels of anti-heat-shock protein 60 (anti-Hsp60) indicate endothelial dysfunction, atherosclerosis and cardiovascular diseases in patients with mixed connective tissue disease |
|
| Edit Bodolay,Zoltan Prohászka,Gyorgy Paragh,Istvan Csipo,Gabor Nagy,Renata Laczik,Nora Demeter,Eva Zöld,Britt Nakken,Gyula Szegedi,Peter Szodoray | | Immunologic Research. 2014; | | [Pubmed] | [DOI] | | | 126 |
Sustained expression of CYPs and DNA adduct accumulation with continuous exposure to PCB126 and PCB153 through a new delivery method: Polymeric implants |
|
| Farrukh Aqil,Hua Shen,Jeyaprakash Jeyabalan,Xing Xin,Hans-Joachim Lehmler,Gabriele Ludewig,Larry W. Robertson,Ramesh C. Gupta | | Toxicology Reports. 2014; 1: 820 | | [Pubmed] | [DOI] | | | 127 |
Lowered plasma paraoxonase (PON)1 activity is a trait marker of major depression and PON1 Q192R gene polymorphism–smoking interactions differentially predict the odds of major depression and bipolar disorder |
|
| Chiara Cristina Bortolasci,Heber Odebrecht Vargas,André Souza-Nogueira,Décio Sabbatini Barbosa,Estefania Gastaldello Moreira,Sandra Odebrecht Vargas Nunes,Michael Berk,Seetal Dodd,Michael Maes | | Journal of Affective Disorders. 2014; 159: 23 | | [Pubmed] | [DOI] | | | 128 |
High Levels of Asymmetric Dimethylarginine Are Strongly Associated with Low HDL in Patients with Acute Myocardial Infarction |
|
| Lorin, J. and Guilland, J.-C. and Korandji, C. and Touzery, C. and Bichat, F. and Chagnon, A. and Cottin, Y. and Rochette, L. and Vergely, C. and Zeller, M. | | PLoS ONE. 2013; 8(6) | | [Pubmed] | | | 129 |
Chlamydophila pneumoniae infection and cardiovascular disease |
|
| Joshi, R. and Khandelwal, B. and Joshi, D. and Gua, O.P. | | North American Journal of Medical Sciences. 2013; 5(3): 169-181 | | [Pubmed] | | | 130 |
Association of carotid plaque echogenicity with recurrence of ischemic stroke |
|
| Singh, A.S. and Atam, V. and Jain, N. and Yathish, B.E. and Patil, M.R. and Das, L. | | North American Journal of Medical Sciences. 2013; 5(6): 371-376 | | [Pubmed] | | | 131 |
Functionally Defective High-Density Lipoprotein and Paraoxonase: A Couple for Endothelial Dysfunction in Atherosclerosis |
|
| Esin Eren,Necat Yilmaz,Ozgur Aydin | | Cholesterol. 2013; 2013: 1 | | [Pubmed] | [DOI] | | | 132 |
High Levels of Asymmetric Dimethylarginine Are Strongly Associated with Low HDL in Patients with Acute Myocardial Infarction |
|
| Julie Lorin,Jean-Claude Guilland,Claudia Korandji,Claude Touzery,Florence Bichat,Aline Chagnon,Yves Cottin,Luc Rochette,Catherine Vergely,Marianne Zeller,Alexander A. Mongin | | PLoS ONE. 2013; 8(6): e64796 | | [Pubmed] | [DOI] | |
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