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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2015

Open Access 01-12-2015 | Original investigation

SIRT1 protects against myocardial ischemia–reperfusion injury via activating eNOS in diabetic rats

Authors: Mingge Ding, Jingyi Lei, Hongcheng Han, Weibo Li, Yinxian Qu, Enqing Fu, Feng Fu, Xiaoming Wang

Published in: Cardiovascular Diabetology | Issue 1/2015

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Abstract

Background

Diabetic patients are more sensitive to myocardial ischemic injury than non-diabetic patients. Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent histone deacetylase making the heart more resistant to ischemic injury. As SIRT1 expression is considered to be reduced in diabetic heart, we therefore hypothesized that up-regulation of SIRT1 in the diabetic heart may overcome its increased susceptibility to ischemic injury.

Methods

Male Sprague–Dawley rats were fed with high-fat diet and injected with streptozotocin once to induce diabetes. Diabetic rats received injections of adenoviral vectors encoding SIRT1 (Ad-SIRT1) at five myocardial sites. Four days after adenoviral injection, the rats were subjected to myocardial ischemia and reperfusion (MI/R). Outcome measures included left ventricular function, infarct size, cellular death and oxidative stress.

Results

Delivery of Ad-SIRT1 into the hearts of diabetic rats markedly increased SIRT1 expression. Up-regulation of SIRT1 in diabetic hearts improved cardiac function and reduced infarct size to the extent as in non-diabetic animals following MI/R, which was associated with reduced serum creatine kinase-MB, lactate dehydrogenase activities and cardiomyocyte apoptosis. Moreover, Ad-SIRT1 reduced the increase in the superoxide generation and malonaldialdehyde content and simultaneously increased the antioxidant capability. Furthermore, Ad-SIRT1 increased eNOS phosphorylation and reduced eNOS acetylation in diabetic hearts. NOS inhibitor L-NAME inhibited SIRT1-enhanced eNOS phosphorylation, and blunted SIRT1-mediated anti-apoptotic and anti-oxidative effects and cardioprotection.

Conclusions

Overexpression of SIRT1 reduces diabetes-exacerbated MI/R injury and oxidative stress via activating eNOS in diabetic rats. The findings suggest SIRT1 may be a promising novel therapeutic target for diabetic cardiac complications.
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Metadata
Title
SIRT1 protects against myocardial ischemia–reperfusion injury via activating eNOS in diabetic rats
Authors
Mingge Ding
Jingyi Lei
Hongcheng Han
Weibo Li
Yinxian Qu
Enqing Fu
Feng Fu
Xiaoming Wang
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2015
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-015-0299-8

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