caa a22 4500 37885223X CHVBK 20180305123326.0 cr unu---uuuuu 161128e20031117xx s 000 0 eng 10.1515/CCLM.2003.222 doi (NATIONALLICENCE)gruyter-10.1515/CCLM.2003.222 Interactions of Homocysteine, Nitric Oxide, Folate and Radicals in the Progressively Damaged Endothelium [Elektronische Daten] [Olaf Stanger, Martin Weger] The endothelium exerts fundamental control over vascular tone, and injury to the endothelium followed by dysfunction is an early key event preceding manifestation of vessel pathology. Both elevated plasma homocysteine and low folate status have been identified as major and independent risk factors for atherosclerosis and have stirred an enormous and still increasing interest. The damaging effects of hyperhomocysteinemia on endothelial function are, at least in part, reversible through folate supplementation. Because of the inverse relationship between plasma folate and homocysteine levels, however, it is difficult to discriminate between their respective effects. Endothelial dysfunction refers mainly to reduced bioavailability of nitric oxide (NO), which is involved in homocysteinemediated vascular damage. Accumulating evidence further suggests that radical oxygen species are fundamentally involved in hyperhomocysteinemia. NO production is determined by cofactors such as tetrahydrobiopterin, which is oxidized and depleted in conditions of oxidant stress by peroxynitrite. Deficiency of tetrahydrofolate contributes to uncoupling, turning the NO synthase into a superoxide radical-producing enzyme. It appears that progression of vascular disease is likely to determine the multiple interactions between homocysteine, NO, oxygen radicals and folate. Folate has only recently been found to exert direct anti-oxidative effects and contribute to restoration of impaired NO metabolism. Understanding of the complex interactions between homocysteine, radicals, NO and folate offers promising perspectives in the individual treatment of vascular disease. Thus, preventive and therapeutic strategies may require a more distinct approach and better discrimination of target groups for greatest possible efficacy. Copyright © 2003 by Walter de Gruyter GmbH & Co. KG Medical equipment & techniques nationallicence Medical diagnosis nationallicence Diseases & disorders nationallicence Stanger Olaf aut Weger Martin aut Clinical Chemistry and Laboratory Medicine Walter de Gruyter 41/11(2003-11-17), 1444-1454 1434-6621 41:11<1444 2003 41 cclm https://doi.org/10.1515/CCLM.2003.222 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/CCLM.2003.222 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Stanger Olaf aut NATIONALLICENCE 700 1- Weger Martin aut NATIONALLICENCE 773 0- Clinical Chemistry and Laboratory Medicine Walter de Gruyter 41/11(2003-11-17), 1444-1454 1434-6621 41:11<1444 2003 41 cclm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter