Cysteine/cystine redox signaling in cardiovascular disease

• Type of Material: Article
• Authors: Young-Mi Kanggo, Emory University; Dean P Jones, Emory University
• Language: English
• Date: 2011-02-15
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.freeradbiomed.2010.11.029
• Title of Journal or Parent Work: Free Radical Biology and Medicine
• ISSN: 0891-5849
• Volume: 50
• Issue: 4
• Start Page: 495
• End Page: 509
• Grant/Funding Information: This work was supported by NIH grants ES011195 and ES009047.
• Keywords: Endothelial cells; Plasma redox state; Inflammatory mechanism; Thiol/disulfide; Monocytes; Atherosclerosis
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Extracellular thiol/disulfide redox environments are highly regulated in healthy individuals. The major thiol/disulfide redox couple in human plasma is cysteine (Cys) and its disulfide form, cystine (CySS). Oxidation of this redox couple measured as a more positive steady-state redox potential (Eh) is associated with risk factors for cardiovascular disease (CVD), including aging, smoking, obesity, and alcohol abuse. Rodent and vascular cell studies show that extracellular redox state of Cys/CySS (EhCySS) can play a vital role in controlling CVD through proinflammatory signaling. This inflammatory signaling is regulated by cell surface protein redox state and involves mitochondrial oxidation, nuclear factor-κB activation, and elevated expression of genes for monocyte recruitment to endothelial cells. Gene array and proteomics studies reveal the global nature of redox effects, and different cell types, e.g., endothelial cells, monocytes, fibroblasts, and epithelial cells, show cell-specific redox responses with different phenotypic traits, e.g., proliferation and apoptosis, which can contribute to CVD. The critical nature of the proinflammatory redox signaling and cell biology associated with EhCySS supports the use of plasma levels of Cys, CySS, and EhCySS as key indicators of vascular health. Plasma redox state-based pharmacologic interventions to control or improve EhCySS may be effective in preventing CVD onset or progression.