Proceedings of the National Academy of Sciences · 2009 · 223 citations · 28 references
Life SciencesBiochemistryCardiologyGene ExpressionMetabolic RegulationRedox BiochemistryAngiogenesisCardiovascular DiseaseCardiovascular Molecular PhysiologyCardiovascular PhysiologyIschemic Heart DiseaseRedox SignalingCardiac Systolic FunctionNitric OxideNitric Oxide BiologyNitric Oxide DonorsOxygenationS-nitrosothiol BiologyVascular Endothelial Growth FactorVentricular Diastolic Function
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.
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Isolation of Putative Progenitor Endothelial Cells for Angiogenesis
Takayuki Asahara, Toyoaki Murohara, Alison Sullivan et al. · Science · 1997 · 8.7K citations