Abstract
Despite substantial evidence that nitric oxide (NO) and/or endogenous 5-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 5-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.
Original language | English (US) |
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Pages (from-to) | 6297-6302 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 106 |
Issue number | 15 |
DOIs | |
State | Published - Apr 14 2009 |
Keywords
- Angiogenesis
- HIF-1α
- Myocardial infarction
- Nitric oxide
- S-nitrosylation
ASJC Scopus subject areas
- General