Atherosclerosis

Aviram, M

doi:10.1097/mol.0b013e3283513594

Cited by 10 publications

(1 citation statement)

References 19 publications

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“…PON1 null mice by gene targeting [12, 13] and transgenic mice [14] corroborate the hypothesis that PON1 protects against atherogenesis and is an important contributor to HDL's antioxidant capacity. The in vivo studies combined with the antioxidant and antiatherogenic nature of PON1 underscore the potential of PON1 as a therapeutic agent to prevent atheroma [20, 21]. The association of PON1 with HDL and its functional consequences support a causal relationship between PON1 and cardiovascular and its associated inflammatory pathologies [22–26].…”

Section: 1 Introductionmentioning

confidence: 99%

Inflammation, Infection, Cancer and All That…The Role of Paraoxonases

Devarajan

Shih

Reddy

2014

Advances in Experimental Medicine and Biology

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The paraoxonase (PON) gene family consists of three members, PON1, PON2 and PON3. All PON proteins possess antioxidant properties and lipo-lactonase activities, and are implicated in the pathogenesis of several inflammatory diseases including atherosclerosis, Alzheimer's, Parkinson's, diabetes and cancer. Despite the role of PON proteins in critical cellular functions and associated pathologies, the physiological substrates and molecular mechanisms by which PON proteins function as anti-inflammatory proteins remain largely unknown. PON1 is found exclusively extracellular and associated solely with high-density lipoprotein (HDL) particles in the circulation, and, in part, confers the anti-oxidant and anti-inflammatory properties associated with HDL. Recent studies demonstrated that the intracellular PON proteins; PON2 and PON3 (i) are associated with mitochondria and mitochondria-associated membranes, (ii) modulate mitochondria-dependent superoxide production, and (iii) prevent apoptosis. Overexpression of PON2 and PON3 genes protected (i) mitochondria from antimycin or oligomycin mediated mitochondrial dysfunction and (ii) ER stress and ER stress mediated mitochondrial dysfunction. These studies illustrate that the anti-inflammatory effects of PON2 and PON3 may, in part, be mediated by their role in mitochondrial and associated organelle function. Since oxidative stress as a result of mitochondrial dysfunction is implicated in the development of inflammatory diseases including atherosclerosis and cancer, these recent studies on PON2 and PON3 proteins may provide a mechanism for the scores of epidemiological studies that show a link between PON genes and numerous inflammatory diseases. Understanding such mechanisms will provide novel routes of intervention in the treatment of diseases associated with pro-inflammatory oxidative stress.

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Section: 1 Introductionmentioning

confidence: 99%

Inflammation, Infection, Cancer and All That…The Role of Paraoxonases

Devarajan

Shih

Reddy

2014

Advances in Experimental Medicine and Biology

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Paraoxonases

Reddy¹

2015

Atherosclerosis

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Selective oxidative stress and cholesterol metabolism in lipid‐metabolizing cell classes: Distinct regulatory roles for pro‐oxidants and antioxidants

Volkova¹,

Aviram²

2015

BioFactors

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Atherogenesis is associated with macrophage cholesterol and oxidized lipids accumulation and foam cell formation. However, two other major lipid-metabolizing cell classes, namely intestinal and liver cells, are also associated with atherogenesis. This study demonstrates that manipulations of cellular oxidative stress (by fatty acids, glucose, low-density lipoprotein, angiotensin II, polyphenolic antioxidants, or the glutathione/paraoxonase 1 systems) have some similar, but also some different effects on cholesterol metabolism in macrophages (J774A.1) versus intestinal cells (HT-29) versus liver cells (HuH7). Cellular oxidative stress was ≈3.5-folds higher in both intestinal and liver cells versus macrophages. In intestinal cells or liver cells versus macrophages, the cholesterol biosynthesis rate was increased by 9- or 15-fold, respectively. In both macrophages and intestinal cells C-18:1 and C-18:2 but not C-18:0, fatty acids significantly increased oxidative stress, whereas in liver cells oxidative stress was significantly decreased by all three fatty acids. In liver cells, trans C-18:1 versus cis C-18:1, unlike intestinal cells or macrophages, significantly increased cellular oxidative stress and cellular cholesterol biosynthesis rate. Pomegranate juice (PJ), red wine, or their phenolics gallic acids or quercetin significantly reduced cellular oxidation mostly in macrophages. Recombinant PON1 significantly decreased macrophage (but not the other cells) oxidative stress by ≈30%. We conclude that cellular atherogenesis research should look at atherogenicity, not only in macrophages but also in intestinal and liver cells, to advance our understanding of the complicated mechanisms behind atherogenesis. © 2015 BioFactors, 41(4):273-288, 2015.

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Atherosclerosis

Cited by 10 publications

References 19 publications

Inflammation, Infection, Cancer and All That…The Role of Paraoxonases

Inflammation, Infection, Cancer and All That…The Role of Paraoxonases

Paraoxonases

Selective oxidative stress and cholesterol metabolism in lipid‐metabolizing cell classes: Distinct regulatory roles for pro‐oxidants and antioxidants

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