Endogenous S-nitrosothiols protect against myocardial injury
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-1α (HIF-1α) under normoxic conditions. We further show that S-nitrosylated HIF-1α 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.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- April 2009
- DOI:
- 10.1073/pnas.0901043106
- Bibcode:
- 2009PNAS..106.6297L
- Keywords:
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- angiogenesis;
- HIF-1α
- myocardial infarction;
- nitric oxide;
- S-nitrosylation;
- Biological Sciences:Medical Sciences