title: Modulation of annexin II by homocysteine: implications for atherothrombosis.
abstract: Recent evidence indicates a potential role for the plasmin/plasminogen activator system in the prevention of atherosclerotic vascular disease. Fibrin deposition is a common histologic feature of the tissues of mice that are genetically deficient in one or more key components of the fibrinolytic system. Cell surface receptors may support fibrinolytic surveillance in both intravascular and extravascular locations by stimulating the efficiency plasmin generation and by protecting plasmin from its inhibitors. In vitro studies suggest that the endothelial cell receptor, annexin II, which independently binds both plasminogen and t-PA, could play a key role in the process. Binding of plasminogen to annexin II is specifically inhibited in the presence of excess concentrations of the atherogenic LDL-like particle Lp(a). Similarly, t-PA binding to annexin II is blocked by homocysteine, a sulfhydryl-containing amino acid that is associated with atherogenesis and that directly derivatizes the t-PA binding domain of annexin II. Elucidation of the precise role of annexin II in fibrinolytic surveillance, however, will await in vivo study.
authors.affiliation: Department of Pediatrics, Cornell University Medical College, New York, NY 10021, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Hajjar
authors.forename: A T
authors.initials: AT
authors.lastname: Jacovina
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D001161:Arteriosclerosis / Q000097:blood* / Q000150:complications; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D006710:Homocysteine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood; D010960:Plasminogen Activators / Q000378:metabolism; D013927:Thrombosis / Q000097:blood* / Q000150:complications
chemical_list: D017306:Annexin A2; D017270:Lipoprotein(a); D006710:Homocysteine; D010960:Plasminogen Activators; D005341:Fibrinolysin