Mitochondrial oxidative stress and heart failure.
Recent experimental and clinical studies have suggested that oxidative stress is enhanced in heart failure. Chronic increases in oxygen radical production in the mitochondria can lead to a catastrophic cycle of mitochondrial DNA (mtDNA) damage as well as functional decline, further oxygen radical generation, and cellular injury. Reactive oxygen species induce myocyte hypertrophy, apoptosis, and interstitial fibrosis by activating matrix metalloproteinases. These cellular events play an important role in the development and progression of maladaptive cardiac remodeling and failure. Overexpression of mitochondrial transcription factor A (TFAM) could ameliorate the decline in mtDNA copy number and preserve it at a normal level in failing hearts. Consistent with alterations in mtDNA, the decrease in oxidative capacities was also prevented. Therefore, the activation of TFAM expression could ameliorate the pathophysiological processes seen in myocardial failure. Inhibition of mitochondrial oxidative stress and DNA damage could be the most effective and novel treatment strategies for heart failure.
Tsutsui
Hiroyuki
H
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo.
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology* / Q000628:therapy; D006609:High Mobility Group Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D020257:Ventricular Remodeling
D000975:Antioxidants; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C499631:TFAM protein, human; C081930:Tfam protein, mouse; D014157:Transcription Factors