Homocysteine and its role in the pathogenesis of atherosclerotic vascular disease.

Homocysteine has been recently recognised as a risk factor for atherosclerotic vascular disease. Numerous studies have studied adverse influence of homocysteine on endothelial cells, vascular smooth muscle cells, connective tissue, interactions with plasma lipoproteins, clotting factors and platelets. It has been suggested that endothelial damage is mediated by hydrogen peroxide, a by-product of auto-oxidation of homocysteine. Human studies have shown that high levels of homocysteine are associated with impaired endothelial dependent vasodilatation in healthy subjects indicating that the bio-availability of nitric oxide (NO) is decreased in those with hyper-homocysteinemia. Homocysteine thialactone (a by-product of homocysteine auto-oxidation) combines with native LDL to form oxidized LDL which is taken up by intimal macrophages to form foam cells which is the beginning of atheromatous plaques. Homocysteine has also influence on proliferation of vascular smooth muscle cells and collagen deposition in atheromatous plaque. In addition several retrospective and prospective studies have shown that hyperhomocysteinaemia is associated with atheromatous and vascular events. Observations in 80 clinical and epidemiological studies have indicated that hyper-homocysteinaemia is a risk factor for atherosclerotic disease. However there are some studies which conclude that homocysteine is not a major risk factor for coronary heart disease.