Docosahexaenoic acid down-regulates endothelial Nox 4 through a sPLA2 signalling pathway

Omega-3 polyunsaturated fatty acids and oxygenated metabolism in atherothrombosis

“…In agreement with our results on 4-HHE, Ishikado et al[120] recently reported that supplementation with dietary fish oil led to increased HHE aortic concentrations and increased the expression of the antioxidant enzyme heme oxygenase-1, and endotheliumdependent vasodilatation. As reviewed very recently[121], potential molecular mechanisms to explain the antioxidant effects of omega-3 fatty acids would be the quenching of ROS as well as direct inhibition of NADPH oxidase 4 (Nox-4) by DHA[122]. Altogether, our results obtained in healthy subjects[67,119,123] reinforce the antioxidant potential of low omega-3 PUFA intake as originally described in elderly subjects displaying increased oxidative stress[60,65] and in dyslipidemic diabetic patients[124].…”

Treatment with n-3 polyunsaturated fatty acids reverses endothelial dysfunction and oxidative stress in experimental menopause

“…Previous in vitro studies using NADPH oxidase inhibitors and mRNA silencing, demonstrated that in fibroblasts NOX-4 is a specific target of DHA modulation, independently from intracellular antioxidant defenses [27]. Exposure of endothelial cells to DHA results in its incorporation into the cell membrane and in the inhibition of NOX-4 expression and activity [40,41]. Experimental evidence also shows that this effect is mediated through endothelial secreted phospholipase A2, ERK and PKC signaling pathways [40,41].…”

“…Exposure of endothelial cells to DHA results in its incorporation into the cell membrane and in the inhibition of NOX-4 expression and activity [40,41]. Experimental evidence also shows that this effect is mediated through endothelial secreted phospholipase A2, ERK and PKC signaling pathways [40,41]. In this study we extend these findings from an in vitro to an in vivo setting, demonstrating that oral treatment with n-3 PUFA in menopause results in their efficient incorporation into plasma membrane, where they blunt oxidative stress by down-regulating NADPH oxidase activity through selective modulation of NOX-4.…”

Nutritional intervention helps pharmacology in the management of the metabolic syndrome

“…Among the most recent evidence there are the observations that docosahexaenoic acid (DHA, 22:6n-3) inhibits endothelial sPLA 2 (it is worth reminding that sPLA 2 is a risk factor for atherosclerosis [10]) via antioxidant actions [11,12] and PKC-mediated pathways [13]. In brief, adequate amounts of omega 3 fatty acids contribute to the amelioration of the metabolic syndrome via multiple pathways such as lowering triglycerides, producing antiinflammatory molecules, and inhibiting pro-inflammatory enzymes [8].…”