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Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 3812568, 16 pages
https://doi.org/10.1155/2018/3812568
Research Article

Hydrogen Sulfide Abrogates Hemoglobin-Lipid Interaction in Atherosclerotic Lesion

1HAS-UD Vascular Biology and Myocardial Pathophysiology Research Group, Hungarian Academy of Sciences, Debrecen 4012, Hungary
2Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen 4012, Hungary
3Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest 1122, Hungary
4Department of Pathology, Faculty of Medicine, University of Debrecen, Debrecen 4012, Hungary
5Division of Nephrology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen 4012, Hungary
6Department of Inorganic and Analytical Chemistry, University of Debrecen, Debrecen 4032, Hungary
7University of Exeter Medical School, Exeter, UK
8College of Life and Environmental Sciences, University of Exeter, Exeter, UK
9Division of Vascular Surgery, Department of Surgery, Faculty of Medicine, University of Debrecen, Debrecen 4012, Hungary

Correspondence should be addressed to József Balla; moc.akinilkleb@allab

Received 2 August 2017; Revised 6 November 2017; Accepted 14 November 2017; Published 21 January 2018

Academic Editor: Kota V. Ramana

Copyright © 2018 László Potor et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The infiltration of red blood cells into atheromatous plaques is implicated in atherogenesis. Inside the lesion, hemoglobin (Hb) is oxidized to ferri- and ferrylHb which exhibit prooxidant and proinflammatory activities. Cystathione gamma-lyase- (CSE-) derived H2S has been suggested to possess various antiatherogenic actions. Expression of CSE was upregulated predominantly in macrophages, foam cells, and myofibroblasts of human atherosclerotic lesions derived from carotid artery specimens of patients. A similar pattern was observed in aortic lesions of apolipoprotein E-deficient mice on high-fat diet. We identified several triggers for inducing CSE expression in macrophages and vascular smooth muscle cells including heme, ferrylHb, plaque lipids, oxidized low-density lipoprotein, tumor necrosis factor-α, and interleukin-1β. In the interplay between hemoglobin and atheroma lipids, H2S significantly mitigated oxidation of Hb preventing the formation of ferrylHb derivatives, therefore providing a novel function as a heme-redox-intermediate-scavenging antioxidant. By inhibiting Hb-lipid interactions, sulfide lowered oxidized Hb-mediated induction of adhesion molecules in endothelium and disruption of endothelial integrity. Exogenous H2S inhibited heme and Hb-mediated lipid oxidation of human atheroma-derived lipid and human complicated lesion. Our study suggests that the CSE/H2S system represents an atheroprotective pathway for removing or limiting the formation of oxidized Hb and lipid derivatives in the atherosclerotic plaque.