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 Hare, Jonathan S. Stamler, Howard A. Rockman

Research output: Contribution to journalArticle

161 Citations (Scopus)

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
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

Fingerprint

S-Nitrosothiols
Hypoxia-Inducible Factor 1
Wounds and Injuries
Vascular Endothelial Growth Factor A
Genes
Ligation
Coronary Vessels
Oxidoreductases
Nitric Oxide
Transcription Factors
Cardiovascular Diseases
Myocardial Infarction

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

Endogenous S-nitrosothiols protect against myocardial injury. / Lima, Brian; Lam, Gregory K W; Xie, Liang; Diesen, Diana L.; Villamizar, Nestor; Nienaber, Jeffrey; Messina, Emily; Bowles, Dawn; Kontos, Christopher D.; Hare, Joshua; Stamler, Jonathan S.; Rockman, Howard A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 15, 14.04.2009, p. 6297-6302.

Research output: Contribution to journalArticle

Lima, B, Lam, GKW, Xie, L, Diesen, DL, Villamizar, N, Nienaber, J, Messina, E, Bowles, D, Kontos, CD, Hare, J, Stamler, JS & Rockman, HA 2009, 'Endogenous S-nitrosothiols protect against myocardial injury', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 15, pp. 6297-6302. https://doi.org/10.1073/pnas.0901043106
Lima, Brian ; Lam, Gregory K W ; Xie, Liang ; Diesen, Diana L. ; Villamizar, Nestor ; Nienaber, Jeffrey ; Messina, Emily ; Bowles, Dawn ; Kontos, Christopher D. ; Hare, Joshua ; Stamler, Jonathan S. ; Rockman, Howard A. / Endogenous S-nitrosothiols protect against myocardial injury. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 15. pp. 6297-6302.
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