Endogenous S-nitrosothiols protect against myocardial injury

Brian Lima, Gregory K W Lam, Liang Xie, Diana L. Diesen, Nestor Villamizar, Jeffrey Nienaber, Emily Messina, Dawn Bowles, Christopher D. Kontos, Joshua M. Hare, Jonathan S. Stamler, Howard A. Rockman

Research output: Contribution to journalArticle

167 Scopus citations

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 languageEnglish (US)
Pages (from-to)6297-6302
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number15
DOIs
StatePublished - Apr 14 2009

Keywords

  • Angiogenesis
  • HIF-1α
  • Myocardial infarction
  • Nitric oxide
  • S-nitrosylation

ASJC Scopus subject areas

  • General

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