caa a22 4500 378852264 CHVBK 20180305123326.0 cr unu---uuuuu 161128e20031117xx s 000 0 eng 10.1515/CCLM.2003.223 doi (NATIONALLICENCE)gruyter-10.1515/CCLM.2003.223 Influence of Hyperhomocysteinemia on the Cellular Redox State - Impact on Homocysteine-Induced Endothelial Dysfunction [Elektronische Daten] [Norbert Weiss, Stanley J. Heydrick, Otilia Postea, Christiane Keller, John F. Keaney, Joseph Loscalzo] Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis. An increasing body of evidence has implicated oxidative stress as being contributory to homocysteine's deleterious effects on the vasculature. Elevated levels of homocysteine may lead to increased generation of superoxide by a biochemical mechanism involving nitric oxide synthase, and, to a lesser extent, by an increase in the chemical oxidation of homocysteine and other aminothiols in the circulation. The resultant increase in superoxide levels is further amplified by homocysteinedependent alterations in the function of cellular antioxidant enzymes such as cellular glutathione peroxidase or extracellular superoxide dismutase. One direct clinical consequence of elevated vascular superoxide levels is the inactivation of the vasorelaxant messenger nitric oxide, leading to endothelial dysfunction. Scavenging of superoxide anion by either superoxide dismutase or 4,5-dihydroxybenzene 1,3-disulfonate (Tiron) reverses endothelial dysfunction in hyperhomocysteinemic animal models and in isolated aortic rings incubated with homocysteine. Similarly, homocysteine-induced endothelial dysfunction is also reversed by increasing the concentration of the endogenous antioxidant glutathione or overexpressing cellular glutathione peroxidase in animal models of mild hyperhomocysteinemia. Taken together, these findings strongly suggest that the adverse vascular effects of homocysteine are at least partly mediated by oxidative inactivation of nitric oxide. Copyright © 2003 by Walter de Gruyter GmbH & Co. KG Medical equipment & techniques nationallicence Medical diagnosis nationallicence Diseases & disorders nationallicence Weiss Norbert aut Heydrick Stanley J. aut Postea Otilia aut Keller Christiane aut Keaney John F. aut Loscalzo Joseph aut Clinical Chemistry and Laboratory Medicine Walter de Gruyter 41/11(2003-11-17), 1455-1461 1434-6621 41:11<1455 2003 41 cclm https://doi.org/10.1515/CCLM.2003.223 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/CCLM.2003.223 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Weiss Norbert aut NATIONALLICENCE 700 1- Heydrick Stanley J. aut NATIONALLICENCE 700 1- Postea Otilia aut NATIONALLICENCE 700 1- Keller Christiane aut NATIONALLICENCE 700 1- Keaney John F. aut NATIONALLICENCE 700 1- Loscalzo Joseph aut NATIONALLICENCE 773 0- Clinical Chemistry and Laboratory Medicine Walter de Gruyter 41/11(2003-11-17), 1455-1461 1434-6621 41:11<1455 2003 41 cclm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter