Antioxidant and anti-inflammatory role of paraoxonase 1: Implication in arteriosclerosis diseases

Litvinov, Dmitry; Mahini, Halleh; Garelnabi, Mahdi

doi:10.4103/1947-2714.103310

Cited by 166 publications

(77 citation statements)

References 56 publications

(69 reference statements)

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“…PON1 is known to play important roles such as an antioxidant, anti-inflammatory, and antiatherosclerotic functions by preventing LDL oxidation [20]. Moreover, PON1 inhibits the accumulation of oxidized LDL and speeds up cholesterol efflux from macrophages [21, 22].…”

Section: Discussionmentioning

confidence: 99%

Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians

Kaur

Bhatti

Vijayvergiya

et al. 2018

Dubai Diabetes Endocrinol J

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Background: Coronary artery disease (CAD) is a complex metabolic disorder in which lifestyle and genetic factors are known to play key roles in pathogenesis. The paraoxonase 1 (PON1) enzyme has a defensive effect against CAD progression, as it safeguards low-density lipoproteins (LDLs) from oxidative modifications. The most extensively studied genetic variants in the PON1 gene are Q192R and L55M, which have been related with LDL antioxidative activity and risk of CAD. Objective: The present case-control study intended to examine the Q192R and L55M polymorphisms and their association with the risk of CAD patients in north Indians. Methods: A total of 872 subjects (412 CAD patients and 460 controls) were recruited from north India. The PON1 gene was amplified and genotypes were studies using PCR-RFLP. χ² analysis was performed to compare genotype/allele frequencies in patients and controls. Results: The present study indicated abdominal obesity, elevated body mass index, and dyslipidemia with increased levels of total cholesterol and triglycerides as well as reduced high-density lipoprotein cholesterol in CAD subjects compared to healthy controls (p < 0.05). Logistic regression analysis of the data revealed an association of the RR genotype of the Q192R polymorphism with an about 2-fold elevated risk of CAD (OR = 2.23, 95% CI = 1.47–3.37, p = 0.0001). Contrariwise, the L55M polymorphism did not show significant association with CAD (OR = 1.81, 95% CI = 0.66–4.95, p = 0.326). Conclusions: The Q192R polymorphism in the PON1 gene may be a susceptibility gene associated with increased risk of CAD in an Asian Indian population.

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Section: Discussionmentioning

confidence: 99%

Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians

Kaur

Bhatti

Vijayvergiya

et al. 2018

Dubai Diabetes Endocrinol J

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“…It is not known whether TLF1 and 2 have functions beyond trypanolysis, and a better understanding of their role in lipid biology may help to elucidate APOL1 function. Subclass HDL3 attenuates low-density lipoprotein oxidation, and APOL1 levels in HDL3 are highly correlated with HDL anti-oxidative function and with presence of paraoxonases 1 and 3 [55], important anti-oxidant and anti-inflammatory proteins [61]. Thus far, all that can be said is that APOL1 is a fellow traveler with anti-oxidant passengers in an anti-inflammatory vehicle; whether APOL1 contributes in any way to these activities remains to be determined.…”

Section: Circulating Apol1 and Lipid Biologymentioning

confidence: 99%

APOL1 Kidney Disease Risk Variants: An Evolving Landscape

Dummer

Limou

Rosenberg

et al. 2015

Seminars in Nephrology

137

125

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APOL1 genetic variants account for much of the excess risk of chronic and end stage kidney disease, which results in a significant global health disparity for persons of African ancestry. We estimate the lifetime risk of kidney disease in APOL1 dual-risk allele individuals to be at least 15%. Experimental evidence suggests a direct role of APOL1 in pore formation, cellular injury, and programmed cell death in renal injury. The APOL1 BH3 motif, often associated with cell death, is unlikely to play a role in APOL1-induced cytotoxicity as it is not conserved within the APOL family and is dispensable for cell death in vitro. We discuss two models for APOL1 trypanolytic activity: one involving lysosome permeabilization and another colloid-osmotic swelling of the cell body, as well as their relevance to human pathophysiology. Experimental evidence from human cell culture models suggests that both mechanisms may be operative. A systems biology approach whereby APOL1-associated perturbations in gene and protein expression in affected individuals are correlated with molecular pathways may be productive to elucidate APOL1 function in vivo.

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“…The anti-oxidant properties of apolipoprotein A-I (apoA-I) (8; 9) as well as other HDL components including paroxonase-1 (PON-1)(10) and platelet-activating factor-acetyl hydrolase (PAF-AH)(3; 11) a are implicated in the prevention of LDL oxidation. Most of the lipid peroxidation products, which have been implicated in both HDL and LDL modification and in the pathogenesis of atherosclerosis are derived from the degradation of the polyunsaturated omega-6 fatty acids, arachidonic acid (AA) and its precursor linoleic acid (LA).…”

Section: Introductionmentioning

confidence: 99%

HDL lipid composition is profoundly altered in patients with type 2 diabetes and atherosclerotic vascular disease

Morgantini

Meriwether

Baldi

et al. 2014

Nutrition, Metabolism and Cardiovascular Diseases

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Background and Aims We have previously shown that the anti-inflammatory and anti-oxidant functions of HDL are impaired in T2D patients. In this study, we examined whether HDL from T2D patients contains elevated levels of oxidized fatty acids and whether those levels correlate with cardiovascular disease (CVD). Methods and Results HETEs and HODEs on HDL were determined by LC-MS/MS in 40 non-diabetic controls (ND), 40 T2D without CVD (D+CVD−) and 38 T2D with known history of CVD (D+CVD+). HDL oxidant index was evaluated by a cell-free assay using dichlorofluorescein. Twenty-six randomly selected subjects from the three groups underwent coronary calcium score evaluation (CAC). Major cardiovascular risk factors were similar among the groups. HETEs and HODEs content were significantly increased in HDL from D+CVD+ when compared to D+CVD− and ND patients. HDL oxidant index was not different among the three groups; however, it was significantly higher in patients with CAC score >100 when compared to patients with CAC score <100. Conclusion Patients with D+CVD− and D+CVD+ are characterized by a severe, graded enrichment of oxidized fatty acids on HDL. In the present study, a loss of HDL function (as estimated by the HDL oxidant index) is observed only in patients with more advanced atherosclerosis.

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Antioxidant and anti-inflammatory role of paraoxonase 1: Implication in arteriosclerosis diseases

Cited by 166 publications

References 56 publications

Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians

Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians

APOL1 Kidney Disease Risk Variants: An Evolving Landscape

HDL lipid composition is profoundly altered in patients with type 2 diabetes and atherosclerotic vascular disease

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