Fish oil supplementation reverses the effect of cholesterol on apoptotic gene expression in smooth muscle cells

An in vivo/in vitro cell model was used, culturing SMC isolated from chicks exposed to an atherogenic cholesterol-rich diet with 5% of cholesterol (SMC-Ch) alone or followed by an anti-atherogenic fish oil-rich diet with 10% of menhaden oil (SMC-Ch-FO) and from chicks on standard diet (SMC-C). Cells were exposed to 25-HC, studying apoptosis levels by flow cytometry (Annexin V) and expressions of caspase-3, c-myc, and p53 genes by quantitative real-time reverse transcriptase-polymerase chain reaction. Results: Exposure to 25-HC produced apoptosis in all three SMC cultures, which was mediated by increases in caspase-3, c-myc, and p53 gene expression. Changes were more marked in SMC-Ch than in SMC-C, indicating that dietary cholesterol makes SMC more susceptible to 25-HC-mediated apoptosis. Expression of p53 gene was elevated in SMC-Ch-FO. This supports the proposition that endogenous levels of p53 protect SMC against apoptosis and possibly against the development of atherosclerosis. Fish oil attenuated the increase in c-myc levels observed in SMC-C and SMC-Ch, possibly through its influence on the expression of antioxidant genes.Replacement of a cholesterol-rich diet with a fish oil-rich diet produces some reversal of the cholesterol-induced changes, increasing the resistance of SMC to apoptosis.Gene expression is influenced by dietary fat [1], gene transcription is regulated by dietary polyunsaturated fatty acids [2], and the nutritional control of gene regulation guides the transformation of SMC into foam cells in atherosclerosis [3]. The present study focused on the effect of cholesterol and fish oil intake on the expression of apoptosis-regulating caspase-3, c-myc and p53 genes.In the 1970 s, a very low incidence of death from ischemic heart disease was observed in Greenland Eskimos, who have a high fish consumption [4]. Evidence from several research lines supports the hypothesis that fish consumption may protect against atherosclerotic vascular disease. Fish oil