Serum paraoxonase-3 concentration is associated with insulin sensitivity in peripheral artery disease and with inflammation in coronary artery disease

Rull, Anna; García, Raúl; Fernández-Sender, Laura; García-Heredia, Anabel; Aragonès, Gerard; Beltrán‐Debón, Raúl; Marsillach, Judit; Alegret, Josep M.; Martín‐Paredero, Vicente; Mackness, Bharti; Mackness, Michael I.; Joven, Jorge; Camps, Jordi

doi:10.1016/j.atherosclerosis.2011.11.021

Cited by 26 publications

(19 citation statements)

References 30 publications

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“…42–45 Additionally, the finding that lower PON3 in HDL correlates with subclinical atherosclerosis contradicts previous studies reporting increased PON3 protein concentrations (as measured by ELISA) in atherosclerosis vs. healthy subjects. 44, 46, 47 One explanation for this apparent discrepancy could be the sample used to determine PON3 concentration, serum in the previous studies and isolated HDL from plasma in the current study. These results are consistent with the proposal that certain HDL particles ( e.g.…”

Section: Discussionmentioning

confidence: 76%

Paraoxonase-3 Is Depleted from the High-Density Lipoproteins of Autoimmune Disease Patients with Subclinical Atherosclerosis

Marsillach¹,

Becker²,

Vaisar³

et al. 2015

J. Proteome Res.

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Patients with autoimmune diseases have a significantly increased risk of developing cardiovascular disease. In disease, high density lipoprotein (HDL) particles lose their anti-inflammatory and antioxidant properties, becoming dysfunctional. The purpose of this study was to test the hypothesis that alterations in the HDL proteomic profile are associated with subclinical atherosclerosis and HDL dysfunction in patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and type 1 diabetes. Targeted proteomics was used to quantify the relative abundance of 18 proteins in HDL from SLE patients with and without atherosclerotic plaque detectable by carotid ultrasound. Changes in the proteomic profile were compared against the in vitro ability of HDL to protect against lipid oxidation. The same proteins were quantified in HDL from patients with type 1 diabetes with or without coronary artery calcification as determined by computed tomography. In each population, paraoxonase-3 (PON3), a potent antioxidant protein, was depleted from the HDL of patients with subclinical atherosclerosis. PON3 expression in HDL was positively correlated with HDL antioxidant function. These results suggest that PON3 may be an important protein in preventing atherosclerosis and highlights the importance of antioxidant proteins in the prevention of atherosclerosis in vivo.

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Section: Discussionmentioning

confidence: 76%

Paraoxonase-3 Is Depleted from the High-Density Lipoproteins of Autoimmune Disease Patients with Subclinical Atherosclerosis

Marsillach¹,

Becker²,

Vaisar³

et al. 2015

J. Proteome Res.

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“…Similar to the result of Lin R et al [24], our study in the southern and northern Han Chinese populations showed insignificant association between SNP rs2071749 in HMOX-1 gene and CAD. Experimental studies also showed that paraoxonases (PONs) including PON1, PON2 and PON3 may prevent low density lipoprotein cholesterol (LDL-C) from peroxidation and play a protective role in atherogenesis [25]. Rull A et al [26].…”

Section: Discussionmentioning

confidence: 99%

NPR-C gene polymorphism is associated with increased susceptibility to coronary artery disease in Chinese Han population: a multicenter study

Liu

Wang

et al. 2016

Oncotarget

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To find a new locus that confers significant susceptibility to CAD in Chinese Han population, a genome-wide association study in 200 “extreme individuals” from a Shandong cohort and a pathway-based candidate gene study from a Shanghai cohort (293 CAD/293 controls) were simultaneously performed. Amongst them, 13 SNPs associated with CAD were selected to conduct validation and replication studies in additional 3363 CAD patients and 3148 controls. A novel locus rs700926 in natriuretic peptide receptor C (NPR-C) was identified in Shandong and Hubei cohorts. Then rs700926 and other nine tag SNPs were genotyped in four geographically different populations (Shandong, Shaanxi, Hubei and Sichuan cohorts), and 6 SNPs (rs700926, rs1833529, rs2270915, rs17541471, rs3792758 and rs696831) showed stronger association with CAD, regardless of single or combined analysis. We further genotyped rs2270915 and 10 additional tag SNPs in a central China cohort and identified rs12697273 and rs10066436 as the loci associated with CAD. All these positive associations remained significant after adjustment for traditional risk factors of CAD. NPR-C gene SNPs significantly contribute to CAD susceptibility in the Chinese Han population.

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“…More recently, six PON3 promoter SNVs in linkage disequilibrium were significantly associated with changes in serum PON3 concentration in a healthy Mediterranean cohort [135]. The same authors studied these six SNVs in human immunodeficiency virus (HIV)-infected patients [136] and in coronary artery disease and peripheral artery disease patients [137]. However, no differences were found in these PON3 gene promoter SNVs and their haplotypes between patients and controls, suggesting that PON3 genotype neither influences serum PON3 concentration nor the course of these human diseases.…”

Section: Pon3mentioning

confidence: 99%

“…Indeed, a significant increase of PON3 concentration has been reported in chronic liver disease [138], HIV-infection [136], and coronary and peripheral artery disease [137]. However, a more recent study in patients with autoimmune disease (systemic lupus erythematosus and type 1 diabetes) has shown significant depletion of PON3 protein in HDLs of patients with autoimmune disease and subclinical atherosclerosis [139].…”

Section: Pon3mentioning

confidence: 99%

Paraoxonases-1, -2 and -3: What are their functions?

Furlong

Marsillach

Jarvik

et al. 2016

Chemico-Biological Interactions

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164

122

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Paraoxonase-1 (PON1), an esterase/lactonase primarily associated with plasma high-density lipoprotein (HDL), was the first member of this family of enzymes to be characterized. Its name was derived from its ability to hydrolyze paraoxon, the toxic metabolite of the insecticide parathion. Related enzymes PON2 and PON3 were named from their evolutionary relationship with PON1. Mice with each PON gene knocked out were generated at UCLA and have been key for elucidating their roles in organophosphorus (OP) metabolism, cardiovascular disease, innate immunity, obesity, and cancer. PON1 status, determined with two-substrate analyses, reveals an individual’s functional Q192R genotype and activity levels. The three-dimensional structure for a chimeric PON1 has been useful for understanding the structural properties of PON1 and for engineering PON1 as a catalytic scavenger of OP compounds. All three PONs hydrolyze microbial N-acyl homoserine lactone quorum sensing factors, quenching Pseudomonas aeruginosa’s pathogenesis. All three PONs modulate oxidative stress and inflammation. PON2 is localized in the mitochondria and endoplasmic reticulum. PON2 has potent antioxidant properties and is found at 3- to 4-fold higher levels in females than males, providing increased protection against oxidative stress, as observed in primary cultures of neurons and astrocytes from female mice compared with male mice. The higher levels of PON2 in females may explain the lower frequency of neurological and cardiovascular diseases in females and the ability to identify males but not females with Parkinson’s disease using a special PON1 status assay. Less is known about PON3; however, recent experiments with PON3 knockout mice show them to be susceptible to obesity, gallstone formation and atherosclerosis. Like PONs 1 and 2, PON3 also appears to modulate oxidative stress. It is localized in the endoplasmic reticulum, mitochondria and on HDL. Both PON2 and PON3 are upregulated in cancer, favoring tumor progression through mitochondrial protection against oxidative stress and apoptosis.

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Serum paraoxonase-3 concentration is associated with insulin sensitivity in peripheral artery disease and with inflammation in coronary artery disease

Cited by 26 publications

References 30 publications

Paraoxonase-3 Is Depleted from the High-Density Lipoproteins of Autoimmune Disease Patients with Subclinical Atherosclerosis

Paraoxonase-3 Is Depleted from the High-Density Lipoproteins of Autoimmune Disease Patients with Subclinical Atherosclerosis

NPR-C gene polymorphism is associated with increased susceptibility to coronary artery disease in Chinese Han population: a multicenter study

Paraoxonases-1, -2 and -3: What are their functions?

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