Atherosclerosis prevention by a fish oil-rich diet in apoE(-/-) mice is associated with a reduction of endothelial adhesion molecules.

Dietary intake of long-chain n-3 polyunsaturated fatty acids (PUFA) reduces the risk for atherosclerosis. Here we examine the effect of a fish oil (FO)-rich diet on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE(-/-)) mice, which are vulnerable because of their high plasma cholesterol and triacylglycerol levels, focusing on the expression of endothelial adhesion molecules. Mice were fed semi-purified diets containing 5% corn oil (CO), rich in n-6 PUFA or menhaden oil as FO, rich in long-chain n-3 PUFA and 0.15% cholesterol after reaching 4 weeks of age, and they were killed when they were 4 weeks, 12 weeks, 18 weeks or 24 weeks old. Oxidative stress in plasma and aortic tissue was not increased in mice fed the FO-rich diet, despite its high peroxidizability index. A reduction of stenosis and intrusion at the aortic root, a decrease in the surface area of atherosclerotic lesions at the aorta and a decrease in P-selectin, vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression were observed in FO-fed mice compared to CO-fed mice. It seems likely that the reduced expression of VCAM-1 and ICAM-1 could be transcriptionally regulated by nuclear factor-kappaB in the aortic root. The protective effect of FO against atherosclerosis was more evident at early ages. In conclusion, FO reduces adhesion molecule expression in lesions in apoE(-/-) mice. Because these molecules are involved in lesion progression the effect of FO may explain the observed decrease in atherogenesis.

Upregulation of endothelial nitric oxide synthase in rat aorta after ingestion of fish oil-rich diet.

A previous study with aortic segments isolated from rats fed a fish oil-rich diet indicated an increase in acetylcholine-induced nitric oxide (.NO)-mediated relaxation. However, it remained to be elucidated whether a fish oil-rich diet affects the vascular activity per se and the point of the.NO-cGMP pathway at which fish oil acts. For this purpose, two groups of Sprague-Dawley rats were fed a semipurified diet containing 5% lipids, either corn oil (CO) or menhaden oil (MO), for 8 wk. We studied the mRNA and protein levels of endothelial NO synthase (eNOS) and NOS activity. The bioavailability of vascular.NO was assessed directly by electron spin resonance spectroscopy. The levels of cGMP, l-arginine, and l-citrulline were also evaluated in homogenates. Superoxide anion (O(2)(-).) production and related antioxidant activities were also studied in aortic segments. The aortic content of eNOS mRNA was increased in rats fed the MO-rich diet. This resulted in increases in both eNOS protein levels (70% relative to the rats fed the CO-rich diet) and NOS activity (102%);.NO production increased by 90%, cGMP levels increased by 100%, and l-arginine decreased by 30%. No change in aortic O(2)(-). production was caused by dietary MO. The upregulation of the eNOS-cGMP pathway induced by dietary MO may contribute to the maintenance of vascular homeostasis and explain its beneficial effect in the prevention of arterial diseases.