Document Detail

Stimulation of glucagon-like-peptide-1 receptor through exendin-4 preserves myocardial performance and prevents cardiac remodeling in infarcted myocardium.
MedLine Citation:
PMID:  25117407     Owner:  NLM     Status:  Publisher    
We have demonstrated that GLP-1 improved myocardial functional recovery in acute myocardial ischemic injury. However, whether stimulation of GLP-1 receptor (GLP-1R) with exendin-4, a selective GLP-1R agonist, could initiate a protective effect in the heart remains to be determined. Mouse myocardial infarction (MI) was created by ligation of the left descending artery. After 48 hrs of MI, animals were divided into the following groups (n=5-7/per group): 1) Sham: animals underwent thoracotomy without ligation; 2) MI: animals that underwent MI and received a daily dose of intraperitoneal injection (i.p.) of saline; 3) MI + exendin-4: infarcted mice received injections of exendin-4 (0.1mg/kg, i.p.). Two weeks later, cardiac function was assessed by echocardiography and an isovolumetrically perfused heart. As compared to control MI hearts, stimulation of GLP-1R improved cardiac function, which was associated with attenuation of myocardial hypertrophy, the mitigation of interstitial fibrosis, an increase in survival rate in post-MI hearts. Furthermore, H9c2 cardiomyoblasts were preconditioned with exendin-4 at a dose of 100 nmol/L, and then were subjected to hydrogen peroxide exposure at the concentrations of 50 μmol/L and 100 μmol/L. The exendin-4-treatment decreased lactate dehydrogenase (LDH) leakage and increased cell survival. Notably, this event was also associated with the reduction of cleaved caspase-3 and caspase-9, attenuation of reactive oxygen species (ROS) production. Exendin-4 treatments improved mitochondrial respiration, suppressed the opening of mitochondrial permeability transition pore (mPTP) and protection of mitochondria function. Our results indicate that GLP-1R serves as a novel approach to eliciting cardioprotection and mitigating oxidative stress-induced injury.
Megan DeNicola; Jianfeng Du; Zhengke Wang; Naohiro Yano; Ling Zhang; Yigang Wang; Gang J Qin; Shougang Zhuang; Ting C Zhao
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-12
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  -     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Journal of Physiology - Endocrinology and Metabolism.
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