Abstract
BackgroundNutritional control of gene regulation guides the transformation of smooth muscle cells (SMC) into foam cells in atherosclerosis. Oxidative stress has been reported in areas of lipid accumulation, activating proliferation genes. Suppression of oxidative stress by antioxidant administration reduces this activation and the progression of lesions. We hypothesized that fish oil consumption may protect against atherosclerotic vascular disease. The study objective was to determine the effects of dietary cholesterol and fish-oil intake on the apoptotic pathways induced by 25-hydroxycholesterol (25-HC) in SMC cultures.MethodsAn 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.ConclusionReplacement 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.
Highlights
Nutritional control of gene regulation guides the transformation of smooth muscle cells (SMC) into foam cells in atherosclerosis
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
Summary
Nutritional control of gene regulation guides the transformation of smooth muscle cells (SMC) into foam cells in atherosclerosis. We hypothesized that fish oil consumption may protect against atherosclerotic vascular disease. 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. Evidence from several research lines supports the hypothesis that fish consumption may protect against atherosclerotic vascular disease. The radical-scavenging ability of F-acids may contribute to the protective properties of fish and fish oil diets against mortality from heart disease. It is well established that menhaden oil supplementation of the diet of chicks produced drastic reductions in plasma cholesterol, VLDL, and low- and high-density lipoprotein (LDL and HDL) fractions [9]. Supplementation of neonate chick diet with 10% menhaden oil for 7 days resulted in a significant hypocholesterolemia and hypotriglyceridemia [11]
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