Research Article
Hydrogen Sulfide Abrogates Hemoglobin-Lipid Interaction in Atherosclerotic Lesion
Figure 9
Proposed protective actions of H2S in the atherosclerotic plaque. (a) Upon infiltration of RBCs into the atherosclerotic lesion erythrocytes are lysed and oxidation of liberated Hb occurs followed by heme release. Oxidized Hb forms and the released heme trigger further lipid peroxidation. FerrylHb exhibits proinflammatory property provoking endothelial cell activation characterized by intercellular gap formation and increased adhesion molecule expression. Endothelial activation facilitates monocyte adhesion and transendothelial migration. (b) In the reactions between Hb and plaque lipids, different oxidized Hb derivatives are formed including metHb and ferrylHb species. Macrophages, foam cells, and smooth muscle cell-derived myofibroblasts respond to such an insult (ferrylHb, heme, plaque lipids, and the proinflammatory cytokines IL-1β and TNF-α) by upregulating CSE expression. The increased production of H2S inhibits (i) oxidation of Hb preventing the formation of ferrylHb derivatives (a novel function as a heme-redox-intermediate-scavenging antioxidant), (ii) oxidation of plaque lipids, and subsequently (iii) activation of endothelium.
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