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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  • Cite this

    Lima, B., Lam, G. K. W., Xie, L., Diesen, D. L., Villamizar, N., Nienaber, J., Messina, E., Bowles, D., Kontos, C. D., Hare, J. M., Stamler, J. S., & Rockman, H. A. (2009). Endogenous S-nitrosothiols protect against myocardial injury. Proceedings of the National Academy of Sciences of the United States of America, 106(15), 6297-6302. https://doi.org/10.1073/pnas.0901043106