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.
journal_name
Proc Natl Acad Sci U S Aauthors
Lima B,Lam GK,Xie L,Diesen DL,Villamizar N,Nienaber J,Messina E,Bowles D,Kontos CD,Hare JM,Stamler JS,Rockman HAdoi
10.1073/pnas.0901043106subject
Has Abstractpub_date
2009-04-14 00:00:00pages
6297-302issue
15eissn
0027-8424issn
1091-6490pii
0901043106journal_volume
106pub_type
杂志文章abstract::The nature of integrated viral DNA in normal and leukemic chicken cells has been studied by sequential nucleic acid hybridization procedures that localize the viral specific DNA in cellular DNA regions differing in reiteration frequency. First, DNA.DNA reassociation was employed to fractionate cellular DNA sequences a...
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