The redox status of aminothiols as a clue to homocysteine-induced vascular damage?

Abstract

Vascular disease associated with increased blood concentrations of homocysteine has been known for many years. However, the pathobiochemical mechanisms leading to vasculopathy are still unknown. Several attempts have been made to establish in vitro model systems for the evaluation of homocysteine specific effects in cultured cells. It was concluded from these experiments, that hyperhomocysteinemia has to be considered as a risk factor for atherosclerosis exerting its effects mainly by mechanisms involving oxidative damage. Here, we summarize the homocysteine induced cellular effects which may be due to alterations of the redox thiol status. Effects specific for homocysteine are demonstrated working on different levels of cellular processes involving protein folding and regulation of nuclear factor κB (NF-kB) controlled gene transcription, the latter opening a new perspective for a novel pathway by which homocysteine might enhance chronic inflammation of the endothelium and possibly contributes to the development of atherosclerosis.