Publications [#162869] of Christopher D. Kontos

Papers Published

1. B Lima, GK Lam, L Xie, DL Diesen, N Villamizar, J Nienaber, E Messina, D Bowles, CD Kontos, JM Hare, JS Stamler, HA Rockman, Endogenous S-nitrosothiols protect against myocardial injury., Proceedings of the National Academy of Sciences of the United States of America, United States, vol. 106 no. 15 (April, 2009), pp. 6297-302, ISSN 1091-6490
   (last updated on 2009/09/06)

   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.

   Keywords:
   Animals • Glutathione Reductase • Heart Injuries • Hela Cells • Humans • Hypoxia-Inducible Factor 1 • Male • Mice • Mice, Inbred C57BL • Mice, Knockout • Protein Binding • S-Nitrosothiols • Time Factors • Transcription, Genetic • Vascular Endothelial Growth Factor A • deficiency • genetics • metabolism • metabolism* • pathology