Scholars@Duke publication: Endogenous S-nitrosothiols protect against myocardial injury.

Endogenous S-nitrosothiols protect against myocardial injury.

Publication , Journal Article

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 in: Proc Natl Acad Sci U S A

April 14, 2009

Published version (DOI) Link to item

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.

Duke Scholars

Author Dawn Elizabeth Bowles Surgery, Surgical Sciences

Author Christopher Dale Kontos Medicine, Cardiology

Author Howard Allan Rockman Medicine, Cardiology

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.0901043106

EISSN

1091-6490

Publication Date

April 14, 2009

Volume

106

Issue

Start / End Page

6297 / 6302

Location

United States

Related Subject Headings

Vascular Endothelial Growth Factor A
Transcription, Genetic
Time Factors
S-Nitrosothiols
Protein Binding
Mice, Knockout
Mice, Inbred C57BL
Mice
Male
Hypoxia-Inducible Factor 1

Citation

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Chicago

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MLA

NLM

Lima, B., Lam, G. K. W., Xie, L., Diesen, D. L., Villamizar, N., Nienaber, J., … Rockman, H. A. (2009). Endogenous S-nitrosothiols protect against myocardial injury. Proc Natl Acad Sci U S A, 106(15), 6297–6302. https://doi.org/10.1073/pnas.0901043106

Lima, Brian, Gregory K. W. Lam, Liang Xie, Diana L. Diesen, Nestor Villamizar, Jeffrey Nienaber, Emily Messina, et al. “Endogenous S-nitrosothiols protect against myocardial injury.” Proc Natl Acad Sci U S A 106, no. 15 (April 14, 2009): 6297–6302. https://doi.org/10.1073/pnas.0901043106.

Lima B, Lam GKW, Xie L, Diesen DL, Villamizar N, Nienaber J, et al. Endogenous S-nitrosothiols protect against myocardial injury. Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6297–302.

Lima, Brian, et al. “Endogenous S-nitrosothiols protect against myocardial injury.” Proc Natl Acad Sci U S A, vol. 106, no. 15, Apr. 2009, pp. 6297–302. Pubmed, doi:10.1073/pnas.0901043106.

Lima B, Lam GKW, Xie L, Diesen DL, Villamizar N, Nienaber J, Messina E, Bowles D, Kontos CD, Hare JM, Stamler JS, Rockman HA. Endogenous S-nitrosothiols protect against myocardial injury. Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6297–6302.

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.0901043106

EISSN

1091-6490

Publication Date

April 14, 2009

Volume

106

Issue

Start / End Page

6297 / 6302

Location

United States

Related Subject Headings

Vascular Endothelial Growth Factor A
Transcription, Genetic
Time Factors
S-Nitrosothiols
Protein Binding
Mice, Knockout
Mice, Inbred C57BL
Mice
Male
Hypoxia-Inducible Factor 1