NDA@SZTAKI

Red cells, hemoglobin, heme, iron, and atherogenesis

Nagy, Emőke

Eaton, John W.

Jeney, ViktĂłria

Soares, Miguel P.

Varga, Zsuzsa

Galajda, Zoltán

SzentmiklĂłsi, JĂłzsef

Méhes, Gábor

Csonka, Tamás

Smith, Ann

Vercellotti, Gregory M.

Balla, György

Balla, JĂłzsef

American Heart Association

2010

RZ Other systems of medicine / orvostudomány egyéb területei

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.

magyar

Article

PeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/62455/1/2010_Nagy_E_Red_cells.pdf

Nagy, Emőke and Eaton, John W. and Jeney, Viktória and Soares, Miguel P. and Varga, Zsuzsa and Galajda, Zoltán and Szentmiklósi, József and Méhes, Gábor and Csonka, Tamás and Smith, Ann and Vercellotti, Gregory M. and Balla, György and Balla, József (2010) Red cells, hemoglobin, heme, iron, and atherogenesis. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 30 (7). pp. 1347-1353. ISSN 1079-5642

http://real.mtak.hu/62455/

https://doi.org/ 10.1161/ATVBAHA.110.206433