Atherogenesis may involve the prooxidant and proinflammatory effects of ferryl hemoglobin

László Potor, Emese Bányai, Gergely Becs, Miguel P. Soares, G. Balla, J. Balla, V. Jeney

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Oxidized cell-free hemoglobin (Hb), including covalently cross-linked Hb multimers, is present in advanced atherosclerotic lesions. Oxidation of Hb produces methemoglobin (Fe 3 +) and ferryl hemoglobin (Fe 4 + = O 2 -). Ferryl iron is unstable and can return to the Fe 3 + state by reacting with specific amino acids of the globin chains. In these reactions globin radicals are produced followed by termination reactions yielding covalently cross-linked Hb multimers. Despite the evanescent nature of the ferryl state, herein we refer to this oxidized Hb as "ferryl Hb." Our aim in this work was to study formation and biological effects of ferrylHb. We demonstrate that ferrylHb, like metHb, can release its heme group, leading to sensitization of endothelial cells (ECs) to oxidant-mediated killing and to oxidation of low-density lipoprotein (LDL). Furthermore, we observed that both oxidized LDL and lipids derived from human atherosclerotic lesions trigger Hb oxidation and subsequent production of covalently cross-linked ferrylHb multimers. Previously we showed that ferrylHb disrupts EC monolayer integrity and induces expression of inflammatory cell adhesion molecules. Here we show that when exposed to ferrylHb, EC monolayers exhibit increased permeability and enhanced monocyte adhesion. Taken together, interactions between cell-free Hb and atheroma lipids engage in a vicious cycle, amplifying oxidation of plaque lipids and Hb. These processes trigger EC activation and cytotoxicity.

Original languageEnglish
Article number676425
JournalOxidative Medicine and Cellular Longevity
DOIs
Publication statusPublished - 2013

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Atherosclerosis
Hemoglobins
Endothelial cells
Endothelial Cells
Oxidation
Globins
Lipids
Monolayers
Methemoglobin
Cell Adhesion Molecules
Atherosclerotic Plaques
Cytotoxicity
Heme
LDL Lipoproteins
Oxidants
Cell Communication
Monocytes
Permeability
Adhesion
Chemical activation

ASJC Scopus subject areas

  • Cell Biology
  • Ageing
  • Biochemistry

Cite this

Atherogenesis may involve the prooxidant and proinflammatory effects of ferryl hemoglobin. / Potor, László; Bányai, Emese; Becs, Gergely; Soares, Miguel P.; Balla, G.; Balla, J.; Jeney, V.

In: Oxidative Medicine and Cellular Longevity, 2013.

Research output: Contribution to journalArticle

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AU - Potor, László

AU - Bányai, Emese

AU - Becs, Gergely

AU - Soares, Miguel P.

AU - Balla, G.

AU - Balla, J.

AU - Jeney, V.

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