title: Homocysteine, intracellular signaling and thrombotic disorders.
abstract: Homocysteine, a sulphur-containing amino acid derived from methionine, has been presented as an independent risk factor for cardiovascular disorders, including atherosclerosis and thrombogenesis. The mechanisms underlying homocysteine-induced effects have been intensively investigated over the last two decades. Homocysteine can induce oxidative stress promoting oxidant injury to vascular and blood cells. Hyperhomocysteinemia often results in intracellular Ca2+ mobilization, endoplasmic reticulum (ER) stress, with the subsequent development of apoptotic events, chronic inflammation leading to endothelial dysfunction and remodeling of the extracellular matrix. Homocysteine has also been reported to induce modulation of gene expression through alteration of the methylation status. The effects of elevated concentrations of circulating homocysteine on the vascular wall, platelet function and coagulation factors promote the development of a pro-coagulant state. The pathophysiological significance of homocysteine in the development of vascular disorders through the induction of endothelial dysfunction and abnormal platelet activity and blood coagulation is discussed in this review.
authors.affiliation: Department of Physiology, University of Extremadura, 10003 Caceres, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Dionisio
authors.forename: I
authors.initials: I
authors.lastname: Jardín
authors.forename: G M
authors.initials: GM
authors.lastname: Salido
authors.forename: J A
authors.initials: JA
authors.lastname: Rosado
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000473:pathology; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications*; D018384:Oxidative Stress; D015398:Signal Transduction; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D006710:Homocysteine