Homocyst(e)ine and heart disease: Pathophysiology of extracellular matrix

Occlusive coronary artery disease is an important factor of cardiovascular morbidity and mortality. The rupture of the thin fibrous cap of the atherom a may be one of the causes of acute coronary syndrome, however, the mechani sm of formation of fibrous plaque are poorly understood. Elevation of plasm a homocysteine, hyperhomocystinemia, H(e), has emerged as an independent ri sk factor for hypertension and fibrotic heart disease. The extracellular ma trix (ECM) components, particularly fibrillar collagen, are elevated in the atherosclerotic Lesions and are the essential integral element in holding the oxidized low density lipoproteins (LDL), homocystine, macrophage and fo am cells in milieu, constituting the primary atherosclerotic and secondary restenotic lesions. In vivo and in vitro physiological, morphological, cell ular, biochemical and molecular experiments have suggested the role of tiss ue homocystine in cardiovascular fibrosis and adverse ECM remodeling follow ing H(e). The tissue homocystine induces cardiovascular fibrosis and may le ad to heart failure via the redox-receptor pathway. The underlying cause an d mechanism of cardiovascular fibrosis associated with arteriosclerosis, at herosclerosis, hypertension and coronary heart disease, involve changes in the levels of tissue redox state.