TY - JOUR
T1 - Physiological and pathological functions of NADPH oxidases during myocardial ischemia-reperfusion
AU - Matsushima, Shouji
AU - Tsutsui, Hiroyuki
AU - Sadoshima, Junichi
N1 - Funding Information:
The authors wish to thank Daniela Zablocki for critical reading of the article and suggestions. This work was supported in part by U.S. Public Health Service Grants HL102738 , HL67724 , HL69020 , HL91469 , AG23039 and AG27211 . This work was also supported by the Fondation Leducq Transatlantic Networks of Excellence . Dr. Matsushima has been supported by a Postdoctoral Fellowship from the Founders Affiliate, American Heart Association.
PY - 2014/7
Y1 - 2014/7
N2 - Oxidative stress, the presence of reactive oxygen species (ROS) in excess of the antioxidant capacity in the heart induces myocardial damage, accumulation of which leads to ischemic heart disease and heart failure. NADPH oxidase (Nox) 2 and 4 are the major sources of O2- and H2O2 in the heart and play a crucial role in the regulation of growth and death in cardiomyocytes. Both Nox2 and Nox4 are upregulated in response to ischemia-reperfusion (I/R), thereby contributing to ROS production and consequent myocardial injury. Suppression of either one of them can reduce ROS and I/R injury in the heart. Importantly, however, a minimum level of ROS production by either Nox2 or Nox4 is essential for the activation of HIF-1α and inhibition of PPARα during I/R, such that combined suppression of both Nox2 and Nox4 exacerbates myocardial I/R injury. Thus, either excessive activation or suppression of Noxs below physiological levels can induce cardiac injury. Here we discuss both detrimental and salutary functions of Nox isoforms during myocardial I/R.
AB - Oxidative stress, the presence of reactive oxygen species (ROS) in excess of the antioxidant capacity in the heart induces myocardial damage, accumulation of which leads to ischemic heart disease and heart failure. NADPH oxidase (Nox) 2 and 4 are the major sources of O2- and H2O2 in the heart and play a crucial role in the regulation of growth and death in cardiomyocytes. Both Nox2 and Nox4 are upregulated in response to ischemia-reperfusion (I/R), thereby contributing to ROS production and consequent myocardial injury. Suppression of either one of them can reduce ROS and I/R injury in the heart. Importantly, however, a minimum level of ROS production by either Nox2 or Nox4 is essential for the activation of HIF-1α and inhibition of PPARα during I/R, such that combined suppression of both Nox2 and Nox4 exacerbates myocardial I/R injury. Thus, either excessive activation or suppression of Noxs below physiological levels can induce cardiac injury. Here we discuss both detrimental and salutary functions of Nox isoforms during myocardial I/R.
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U2 - 10.1016/j.tcm.2014.03.003
DO - 10.1016/j.tcm.2014.03.003
M3 - Review article
C2 - 24880746
AN - SCOPUS:84904043432
SN - 1050-1738
VL - 24
SP - 202
EP - 205
JO - Trends in Cardiovascular Medicine
JF - Trends in Cardiovascular Medicine
IS - 5
ER -