Redox regulation of angiotensin II signaling in the heart.
A large number of studies have demonstrated the role of angiotensin II in cardiac preconditioning against ischemic reperfusion injury. Generally, angiotensin II is a detrimental factor for the heart, and its inhibition with an ACE inhibitor provides cardioprotection. This review provides an explanation for such paradoxical behavior of angiotensin II. Angiotensin II can potentiate the induction of the expression of a variety of redox-sensitive factors including p38 MAPK, JNK and Akt, IGF-IR, EGF-R, and HO-1 as well as redox-regulated genes and transcription factors such as NFkappaB. It becomes increasingly apparent that during the earlier phase, the heart attempts to adapt itself against the detrimental effects of angiotensin II by upregulating several cardioprotective genes and proteins. These genes and proteins are redox-regulated and the antioxidants or ROS scavengers block their expressions. Interestingly, an identical pattern of cardioprotective proteins and genes are expressed in the preconditioned heart, which are also inhibited with ROS scavengers. It is tempting to speculate that the induction of the expression of the redox-sensitive cardioprotective proteins is the results of adaptation of the heart against the oxidative stress resulting from angiotensin II; and preconditioning is the net result of harnessing its own protection during ischemic and/or oxidative stress through its ability to trigger redox signaling.
Das
Dipak K
DK
Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1110, USA. DDAS@NEURON.UCHC.EDU
Maulik
Nilanjana
N
Engelman
Richard M
RM
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D006321:Heart / Q000502:physiology; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D015398:Signal Transduction
D017382:Reactive Oxygen Species; D000804:Angiotensin II