Document Detail


Effects of PP1-12, a Novel Protein Phosphatase-1 Inhibitor, on Ventricular Function and Remodeling After Myocardial Infarction in Rats.
MedLine Citation:
PMID:  25286361     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
: PP1-12, a new protein phosphatase-1 inhibitor, is designed and synthesized to modulate the endoplasmic reticulum (ER) stress apoptotic pathway, which is involved in various cardiovascular diseases. In this study, we examined the effect of PP1-12 on ventricular remodeling and heart function after myocardial infarction. Rats that survived within 24 hours after coronary ligation were randomly divided into 6 groups and treated with normal saline, vehicle, PP1-12 at 1, 3, and 10 mg·kg·d and perindopril at 2 mg·kg·d for 4 weeks, respectively. At the end of the follow-up point, we evaluated echocardiographic and hemodynamic parameters, myocardial pathomorphology, apoptosis, and interstitial fibrosis, as well as the expression levels of important proteins involved in ER stress and apoptosis. Left ventricular geometry and function were ameliorated by PP1-12. PP1-12 inhibited interstitial fibrosis and reduced apoptosis of cardiomyocytes in a dose-dependent manner. PP1-12 decreased GRP78 and caspase-12 expression and increased p-eIF2α and Bcl-2/Bax expression. These results suggest that PP1-12 efficiently inhibits left ventricular remodeling and improves heart function. The mechanism involved may be associated with the ability of PP1-12 to depress myocardial apoptosis induced by ER stress.
Authors:
Yun-Yun He; Chun-Lei Liu; Xin Li; Wu Zhong; Song Li; Kun-Lun He; Li-Li Wang
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  64     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  360-7     Citation Subset:  IM    
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