Vascular dysfunction in hyperhomocyst(e)inemia. Implications for atherothrombotic disease

Elevated plasma homocyst(e)ine is currently accepted as a major, independent risk factor for atherosclerosis and venous thrombosis. Even moderate hyperhomocyst(e)inemia is prospectively associated with increased risk of mortality in patients with cardiovascular disease. However, the underlying mechanisms resulting in vascular damage are not clearly defined. The endothelium exerts fundamental control on the vascular tone, coagulation and fibrinolysis. Injury to the endothelium followed by dysfunction is an early key event preceding manifestation of vessel pathology. Acute and chronic exposure of endothelium to homocyst(e)ine induces impairment of endothelial function associated with altered homeostasis and morphologic changes of the vessel wall. Investigations of the role of homocyst(e)ine in the endothelium-dependent function in healthy subjects and cardiovascular patients have recently added important clinical insight with implications for the treatment of cardiovascular disease. Importantly, the damaging effects of hyperhomocyst(e)inemia on endothelial function are, at least in part, reversible in patients with established vascular disease, supporting further the hypothesis that homocyst(e)ine-lowering through vitamin supplementation may have vasoprotective effects.