Atherosclerosis risk factors: the possible role of homocysteine

Atherosclerosis is the leading cause of death in North America. It is chara cterized by thickening of the coronary artery wall by the formation of plaq ues, resulting in reduced blood flow. Plaque rupture and the consequent thr ombosis may lead to sudden blockage of arteries and causing stroke and hear t attack. In the last several decades, more than 250 factors associated wit h the development of coronary artery disease have been identified. Recently , a relationship between atherosclerosis and elevated homocysteine level in the blood has been established. The mechanism for the production of athero sclerosis by homocysteine has been investigated. When human hepatoma cells (HepG2) were incubated with 4mM homocysteine, enhancements in the productio n of cholesterol and secretion of apolipoprotein B-100 were observed. The s timulatory effect on cholesterol synthesis was mediated via the enhancement of HMG-CoA reductase, which catalyzes the rate-limiting step in cholestero l biosynthesis. Cholesterol appears to play an important role in the regula tion of apoB-100 secretion by hepatocytes. It is plausible that the increas e in apoB secretion was caused by the elevated cholesterol level induced by homocysteine. The ability of homocysteine to produce a higher amount of ch olesterol and promote the secretion of apoB would provide a plausible mecha nism for the observed relationship between hyperhomocysteinemia and the dev elopment of atherogenesis and coronary artery disease.