Physiological Studies on the Risk Factors Responsible for Atherosclerosis in Rats

Despite the well established correlation between hypercholesterolemia and coronary artery disease (CAD), a substantial body of evidence challenge this relationship. The study aimed to examine whether hyperlipidemia per se constitutes the principal risk factor for atherosclerosis or just a coordinator to other critical mediators. Hyperlipidemia was produced by feeding rats with high-fat diet for two months. The occurrence of hyperlipidemia was determined by measuring lipid profile. The hyperlipidemic rats were subdivided into two groups i) hyperlipidemic rats ii) hyperlipidemic rats injected with single dose of Escherichia coli (E. Coli) (and kept for two weeks to develop bacteremia and its subsequent effects. Result showed that hyperlipidemia significantly increased total cholesterol, triglycerides, low density lipoprotein (LDL) and homocysteine levels, whereas decreased high density lipoprotein cholesterol (HDL) levels. Moreover, hyperlipidemia induced mild oxidative stress in terms of elevated levels of malondialdehyde (MDA) and nitric oxide (NO) and decreased level of reduced glutathione (GSH) in blood. In addition, hyperlipidemic rats exhibited high plasma viscosity, altered hematological indices and caused histological abnormalities manifested as perivascular hemorrhage, vacuolation of the tunica media and minor thickening in aorta wall. Bacteremia provoked inflammatory reactions and oxidative stress, elevated plasma homocysteine and caused noticeable considerable thickening of media-intema layer suggesting the commencement of atherosclerosis. Hyperlipidemic-bacteremic rats showed an additive effect. The study indicated that although hyperlipidemia is an apparent risk factor, homocysteinmia, the inflammatory component and the oxidative stress emerge to be the underlying mechanisms of atherosclerosis pathogenesis. [Nature and Science 2010;8(5):144-151]. (ISSN: 1545-0740).