title: Oxidative stress in heart failure: what are we missing?
abstract: Over the past several decades, investigations in humans and animal models of heart failure (HF) have provided substantial evidence that oxidative stress is increased in HF and contributes to disease progression. The high metabolic activity of cardiac myocytes makes these cells active sources of reactive oxygen species. Work in cell and animal models clearly demonstrates that oxidative stress activates processes such as changes in gene expression and cell death that are now accepted components of myocardial remodeling and HF. Antioxidants prevent progressive remodeling and even improve cardiac function in animal models of HF. It is therefore disappointing that to date no antioxidant strategy has translated to a therapeutic in the HF clinic. Possible explanations, including inadequate appreciation of the critical disease-modifying sources of reactive oxygen species, the choice of the wrong antioxidant strategy, or incomplete understanding of individual variability in human antioxidant defenses in this brief review.
authors: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. douglas.b.sawyer@vanderbilt.edu
authors: Douglas B
authors: DB
authors: Sawyer
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D016923:Cell Death; D018450:Disease Progression; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D014810:Vitamin E; D019001:Nitric Oxide Synthase