title: The role of oxidative stress in the metabolic syndrome.
abstract: Loss of reduction-oxidation (redox) homeostasis and generation of excess free oxygen radicals play an important role in the pathogenesis of diabetes, hypertension, and consequent cardiovascular disease. Reactive oxygen species are integral in routine in physiologic mechanisms. However, loss of redox homeostasis contributes to proinflammatory and profibrotic pathways that promote impairments in insulin metabolic signaling, reduced endothelial-mediated vasorelaxation, and associated cardiovascular and renal structural and functional abnormalities. Redox control of metabolic function is a dynamic process with reversible pro- and anti-free radical processes. Labile iron is necessary for the catalysis of superoxide anion, hydrogen peroxide, and the generation of the damaging hydroxyl radical. Acute hypoxia and cellular damage in cardiovascular tissue liberate larger amounts of cytosolic and extracellular iron that is poorly liganded; thus, large increases in the generation of oxygen free radicals are possible, causing tissue damage. The understanding of iron and the imbalance of redox homeostasis within the vasculature is integral in hypertension and progression of metabolic dysregulation that contributes to insulin resistance, endothelial dysfunction, and cardiovascular and kidney disease.
authors.affiliation: Diabetes and Cardiovascular Center, Harry S. Truman VA Medical Center, Columbia, MO, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Whaley-Connell
authors.forename: Peter A
authors.initials: PA
authors.lastname: McCullough
authors.forename: James R
authors.initials: JR
authors.lastname: Sowers
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000627:therapeutic use; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D007501:Iron