Oxidative Stress and Mitochondrial DNA Damage in Heart Failure

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Author(s)

    • TSUTSUI Hiroyuki
    • Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine
    • KINUGAWA Shintaro
    • Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine
    • MATSUSHIMA Shouji
    • Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine

Abstract

Recent experimental and clinical studies have suggested that oxidative stress is enhanced in heart failure. The production of oxygen radicals is increased in the failing heart while antioxidant enzyme activities are preserved. Mitochondrial electron transport is an enzymatic source of oxygen radical generation and also a target against oxidant-induced damage in the failing myocardium. 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. Therefore, oxidative stress and mtDNA damage are good therapeutic targets. Overexpression of peroxiredoxin-3 (Prx-3), mitochondrial antioxidant, or mitochondrial transcription factor A (TFAM) could ameliorate the decline in mtDNA copy number in failing hearts. Consistent with alterations in mtDNA, the decrease in oxidative capacities is also prevented. Therefore, the activation of Prx-3 or TFAM expression could ameliorate the pathophysiological processes seen in myocardial failure. Inhibition of oxidative stress and mtDNA damage could be novel and potentially effective treatment strategies for heart failure. (<i>Circ J</i> 2008; <b>Suppl A:</b> A-31 - A-37)<br>

Journal

  • Circulation Journal

    Circulation Journal 72, "A-31"-"A-37", 2008-09-20

    Japanese Circulation Society

References:  63

Cited by:  8

Codes

  • NII Article ID (NAID)
    110006935629
  • NII NACSIS-CAT ID (NCID)
    AA11591968
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    13469843
  • Data Source
    CJP  CJPref  NII-ELS  J-STAGE 
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