title: Endogenous S-nitrosothiols protect against myocardial injury.
abstract: 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.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Lima
authors.forename: Gregory K W
authors.initials: GK
authors.lastname: Lam
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
authors.forename: Diana L
authors.initials: DL
authors.lastname: Diesen
authors.forename: Nestor
authors.initials: N
authors.lastname: Villamizar
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Nienaber
authors.forename: Emily
authors.initials: E
authors.lastname: Messina
authors.forename: Dawn
authors.initials: D
authors.lastname: Bowles
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Kontos
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Stamler
authors.forename: Howard A
authors.initials: HA
authors.lastname: Rockman