期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 30, 期 7, 页码 1347-U190出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.110.206433
关键词
atherosclerosis; hemoglobin; oxidized lipids; reactive oxygen species; heme; heme-oxygenase-1
资金
- Hungarian Government [OTKA-K61546, OTKA-K75883, ETT-337/2006, ETT-147/2009, RET-06/2004, MTA-DE-11003]
- Commonwealth of Kentucky Research Challenge Trust [NIH DK073586]
- European Commission [PEOPLE-2007-2-1-IEF]
- Fundacao para a Ciencia e a Tecnologia, Portugal [POCTI/BIA-BCM/56829/2004, POCTI/SAU-MNO/56066/2004, POCTI/SAU/56066/2007]
- XENOME [LSHB-CT-2006037377]
- GEMI fund (Linde Health care)
- University of Missouri at Kansas City Research Incentive
- NIH [NHLBI R01-HL67367, P01-HL055552]
Objective-We investigated whether red cell infiltration of atheromatous lesions promotes the later stages of atherosclerosis. Methods and Results-We find that oxidation of ferro (FeII) hemoglobin in ruptured advanced lesions occurs generating ferri (FeIII) hemoglobin and via more extensive oxidation ferrylhemoglobin (FeIII/FeIV = O). The protein oxidation marker dityrosine accumulates in complicated lesions, accompanied by the formation of cross-linked hemoglobin, a hallmark of ferrylhemoglobin. Exposure of normal red cells to lipids derived from atheromatous lesions causes hemolysis and oxidation of liberated hemoglobin. In the interactions between hemoglobin and atheroma lipids, hemoglobin and heme promote further lipid oxidation and subsequently endothelial reactions such as upregulation of heme oxygenase-1 and cytotoxicity to endothelium. Oxidative scission of heme leads to release of iron and a feed-forward process of iron-driven plaque lipid oxidation. The inhibition of heme release from globin by haptoglobin and sequestration of heme by hemopexin suppress hemoglobin-mediated oxidation of lipids of atheromatous lesions and attenuate endothelial cytotoxicity. Conclusion-The interior of advanced atheromatous lesions is a prooxidant environment in which erythrocytes lyse, hemoglobin is oxidized to ferri-and ferrylhemoglobin, and released heme and iron promote further oxidation of lipids. These events amplify the endothelial cell cytotoxicity of plaque components. (Arterioscler Thromb Vasc Biol. 2010; 30: 1347-1353.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据