Possible involvement of sulfane sulfur in homocysteine-induced atherosclerosis

Abstract 

Homocysteinemia, first identified as a genetic disease in children in the 1960s, is associated with severe widespread atherosclerosis which causes death (in untreated cases) before the age of 10 years. Elevated blood homocysteine is now recognized as a risk factor for heart disease in the general population. The mechanism by which homocysteine induces atherosclerosis is still unknown despite intensive investigation. It is proposed here that the mechanism involves sulfane sulfur formed in the catabolism of homocysteine. This unstable and reactive form of sulfur is formed through the action of several enzymes which are known to use homocysteine, its disulfide (homocystine), or its mixed disulfide with cysteine as substrates. Sulfane sulfur has physiological effects which are consistent with a role in atherogenesis. At very low concentrations, it induces proliferation of many cell types, an effect which is consistent with the fibrosis and hyperplasia, which are prominent features of atherosclerotic lesions. At higher concentrations, it is toxic. Also, it modulates the activity of many enzymes and, through this effect on enzymes of lipid metabolism, it could be responsible for the lipid accumulation seen in atherosclerotic lesions.

No full text is available. To read the body of this article, please view the PDF online.