Cysteine/cystine redox signaling in cardiovascular disease.
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 (E(h)), is associated with risk factors for cardiovascular disease (CVD), including aging, smoking, obesity, and alcohol abuse. Rodent and vascular cell studies show that the extracellular redox state of Cys/CySS (E(h)CySS) 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 E(h)CySS supports the use of plasma levels of Cys, CySS, and E(h)CySS as key indicators of vascular health. Plasma redox-state-based pharmacologic interventions to control or improve E(h)CySS may be effective in preventing CVD onset or progression.
Department of Medicine, Emory University, Atlanta, GA 30322, USA. ygo@emory.edu
Young-Mi
YM
Go
Dean P
DP
Jones
D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism*; D003545:Cysteine / Q000097:blood / Q000378:metabolism*; D003553:Cystine / Q000097:blood / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015398:Signal Transduction
D003553:Cystine; D003545:Cysteine