Endothelin-1 mRNA and protein in vascular wall cells is increased by reactive oxygen species.
A dysregulated metabolism of oxygen-derived free radicals, nitric oxide and endothelin-1(ET-1) in conditions such as hypercholesterolaemia or hypertension may promote the development of atherosclerosis. We therefore subjected cultured human umbilical vein endothelial cells and coronary artery smooth muscle cells to oxidative stress induced by xanthine oxidase or hydrogen peroxide and observed alterations in ET-1 metabolism. Incubation with oxygen-derived free radicals increased preproET-1 promoter activity, ET-1 mRNA synthesis and big ET-1 concentrations in both cell types. This interaction of oxidative stress and ET-1 expression may be relevant in atherogenic conditions such as hypercholesterolaemia and hypertension since our data indicate that oxidative stress further aggravates the injurious effects attributed to ET-1.
Kaehler
Jan
J
Department of Cardiology, University Hospital Hamburg, Martinistr. 52, 20246 Hamburg, Germany. kaehler@uke.uni-hamburg.de
Sill
Bjoern
B
Koester
Ralf
R
Mittmann
Clemens
C
Orzechowski
Hans-Dieter
HD
Muenzel
Thomas
T
Meinertz
Thomas
T
D002478:Cells, Cultured; D003331:Coronary Vessels; D019332:Endothelin-1 / Q000235:genetics* / Q000378:metabolism*; D016232:Endothelins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014471:Umbilical Veins; D014969:Xanthine Oxidase / Q000494:pharmacology
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase