Mitochondrial oxidative stress, DNA damage, and heart failure

Hiroyuki Tsutsui, Tomomi Ide, Shintaro Kinugawa

Research output: Contribution to journalReview article

103 Citations (Scopus)

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, whereas antioxidant enzyme activities are preserved as normal. Mitochondrial electron transport is an enzymatic source of oxygen radical generation and also a target of oxidant-induced damage. 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, mitochondrial oxidative stress and mtDNA damage are good therapeutic targets. 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 pathophysiologic processes seen in myocardial failure. Inhihition of mitochondrial oxidative stress and mtDNA damage could be novel and potentially very effective treatment strategies for heart failure.

Original languageEnglish
Pages (from-to)1737-1744
Number of pages8
JournalAntioxidants and Redox Signaling
Volume8
Issue number9-10
DOIs
Publication statusPublished - Sep 1 2006

Fingerprint

Oxidative stress
Mitochondrial DNA
DNA Damage
Reactive Oxygen Species
Oxidative Stress
Heart Failure
DNA
Mitochondria
Enzyme activity
Electron Transport
Matrix Metalloproteinases
Oxidants
Muscle Cells
Hypertrophy
Fibrosis
Antioxidants
Chemical activation
Apoptosis
Wounds and Injuries
Enzymes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Mitochondrial oxidative stress, DNA damage, and heart failure. / Tsutsui, Hiroyuki; Ide, Tomomi; Kinugawa, Shintaro.

In: Antioxidants and Redox Signaling, Vol. 8, No. 9-10, 01.09.2006, p. 1737-1744.

Research output: Contribution to journalReview article

@article{49d0c063e3f548958dc20ae697d7cf91,
title = "Mitochondrial oxidative stress, DNA damage, and heart failure",
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, whereas antioxidant enzyme activities are preserved as normal. Mitochondrial electron transport is an enzymatic source of oxygen radical generation and also a target of oxidant-induced damage. 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, mitochondrial oxidative stress and mtDNA damage are good therapeutic targets. 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 pathophysiologic processes seen in myocardial failure. Inhihition of mitochondrial oxidative stress and mtDNA damage could be novel and potentially very effective treatment strategies for heart failure.",
author = "Hiroyuki Tsutsui and Tomomi Ide and Shintaro Kinugawa",
year = "2006",
month = "9",
day = "1",
doi = "10.1089/ars.2006.8.1737",
language = "English",
volume = "8",
pages = "1737--1744",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "9-10",

}

TY - JOUR

T1 - Mitochondrial oxidative stress, DNA damage, and heart failure

AU - Tsutsui, Hiroyuki

AU - Ide, Tomomi

AU - Kinugawa, Shintaro

PY - 2006/9/1

Y1 - 2006/9/1

N2 - 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, whereas antioxidant enzyme activities are preserved as normal. Mitochondrial electron transport is an enzymatic source of oxygen radical generation and also a target of oxidant-induced damage. 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, mitochondrial oxidative stress and mtDNA damage are good therapeutic targets. 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 pathophysiologic processes seen in myocardial failure. Inhihition of mitochondrial oxidative stress and mtDNA damage could be novel and potentially very effective treatment strategies for heart failure.

AB - 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, whereas antioxidant enzyme activities are preserved as normal. Mitochondrial electron transport is an enzymatic source of oxygen radical generation and also a target of oxidant-induced damage. 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, mitochondrial oxidative stress and mtDNA damage are good therapeutic targets. 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 pathophysiologic processes seen in myocardial failure. Inhihition of mitochondrial oxidative stress and mtDNA damage could be novel and potentially very effective treatment strategies for heart failure.

UR - http://www.scopus.com/inward/record.url?scp=33750915424&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750915424&partnerID=8YFLogxK

U2 - 10.1089/ars.2006.8.1737

DO - 10.1089/ars.2006.8.1737

M3 - Review article

C2 - 16987026

AN - SCOPUS:33750915424

VL - 8

SP - 1737

EP - 1744

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 9-10

ER -