- Author
- Lima B,Lam GK,Xie L,Diesen DL,Villamizar N,Nienaber J,Messina E,Bowles D,Kontos CD,Hare JM,Stamler JS,Rockman HA
- Title
- Endogenous S-nitrosothiols protect against myocardial injury.
- Publication Date
- 3/26/2009
- Pages
- -
- Journal Name
- Proceedings of the National Academy of Sciences of the United States of America
- Abstract
- Despite substantial evidence that nitric oxide (NO) and/or endogenous S-nitrosothiols (SNOs) exert protective effects in a variety of cardiovascular diseases, the molecular details are largely unknown. Here we show that following left coronary artery ligation, mice with a targeted deletion of the S-nitrosoglutathione reductase gene (GSNOR(-/-)) have reduced myocardial infarct size, preserved ventricular systolic and diastolic function, and maintained tissue oxygenation. These profound physiological effects are associated with increases in myocardial capillary density and S-nitrosylation of the transcription factor hypoxia inducible factor-1alpha (HIF-1alpha) under normoxic conditions. We further show that S-nitrosylated HIF-1alpha binds to the vascular endothelial growth factor (VEGF) gene, thus identifying a role for GSNO in angiogenesis and myocardial protection. These results suggest innovative approaches to modulate angiogenesis and preserve cardiac function.
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