Dietary supplements in polyunsaturated fatty acids (PUFA), particularly omega-3, are well known for the beneficial role that they play in preventing cardiovascular diseases. The aim of this study was to determine the role of PUFA on the modulation of apoptosis induced by hypochlorous acid oxidized LDL (HOCl-oxLDL) in U937 monocytic cell lines, and the impact on atherosclerosis in Apolipropotein E-knockout (ApoE-/-) mice.
We tested the potential effect on modulation of HOCl-oxLDL-induced apoptosis after a cellular membrane overloading with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (ARA) or oleic acid (OA). We showed that both EPA and ARA, exerted a pro-apoptotic effect through a specific activation of the intrinsic mitochondrial apoptotic pathway including an increase in DNA fragmentation, a specific activation of caspase activity and protein expression and a loss of mitochondrial membrane potential. In parallel, three groups of ApoE-/- mice were fed on diet supplemented with EPA, or DHA, or not, for 5- or 12-weeks. Whatever the treatment, serum cholesterol concentrations were similar in the three groups and PUFA supplementation do not appeared to prevent development of atherosclerotic plaques measured by oil red O-staining of descending aorta or aortic sinus.
These data demonstrate a novel function of dietary supplements in PUFA with likely consequences in apoptosis in cultured monocytes, with no protection against atherosclerosis development in ApoE-/- mice.Le texte complet de cet article est disponible en PDF.