Homocyst(E)Ine and Heart Disease: Pathophysiology of Extracellular Matrix

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Abstract
Occlusive coronary artery disease is an important factor of cardiovascular morbidity and mortality. The rupture of the thin fibrous cap of the atheroma may be one of the causes of acute coronary syndrome, however, the mechanism of formation of fibrous plaque are poorly understood. Elevation of plasma homocysteine, hyperhomocystinemia, H(e), has emerged as an independent risk factor for hypertension and fibrotic heart disease. The extracellular matrix (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 foam cells in milieu, constituting the primary atherosclerotic and secondary restenotic lesions. In vivo and in vitro physiological, morphological, cellular, biochemical and molecular experiments have suggested the role of tissue homocystine in cardiovascular fibrosis and adverse ECM remodeling following H(e). The tissue homocystine induces cardiovascular fibrosis and may lead to heart failure via the redox-receptor pathway. The underlying cause and mechanism of cardiovascular fibrosis associated with arteriosclerosis, atherosclerosis, hypertension and coronary heart disease, involve changes in the levels of tissue redox state.