Modulation of apoptosis by nitric oxide: implications in myocardial ischemia and heart failure.
The purpose of this review is to summarize the regulation of apoptosis by nitric oxide (NO) and to discuss the potential role that NO plays in cardiomyocyte apoptosis during myocardial ischemia/reperfusion and development of heart failure. NO is an important regulator of apoptosis within the mammalian system, capable of both inducing and preventing apoptosis, depending upon the level of NO production and environmental milieu. This bifunctional capacity is well illustrated in the heart. It appears that high levels of NO produced by inducible nitric oxide synthase (iNOS) promote apoptosis while basal levels of NO production from endothelial nitric oxide synthase (eNOS) protect cardiomyocytes from apoptosis. Since permanent loss of cardiomyocytes due to apoptosis contributes to the development of heart failure, inhibition of cardiomyocyte apoptosis may have therapeutic implications. Given its pro- and anti-apoptotic capacity within the heart, NO may serve as a valuable therapeutic target in myocardial ischemia and heart failure.
Razavi
Habib M
HM
Victoria Research Laboratories, 6th Floor, Lawson Health Research Institute, London Health Sciences Centre, Department of Medicine, University of Western Ontario, 800 Commissioners Road, London, Ontario, Canada N6A 4G5.
Hamilton
Joel A
JA
Feng
Qingping
Q
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II
D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D020169:Caspases