Endogenous S-nitrosothiols protect against myocardial injury.

Published

Journal Article

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-1alpha (HIF-1alpha) under normoxic conditions. We further show that S-nitrosylated HIF-1alpha 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.

Full Text

Duke Authors

Cited Authors

  • Lima, B; Lam, GKW; Xie, L; Diesen, DL; Villamizar, N; Nienaber, J; Messina, E; Bowles, D; Kontos, CD; Hare, JM; Stamler, JS; Rockman, HA

Published Date

  • April 2009

Published In

Volume / Issue

  • 106 / 15

Start / End Page

  • 6297 - 6302

PubMed ID

  • 19325130

Pubmed Central ID

  • 19325130

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0901043106

Language

  • eng