Document Detail


Rosuvastatin enhances the therapeutic efficacy of adipose-derived mesenchymal stem cells for myocardial infarction via PI3K/Akt and MEK/ERK pathways.
MedLine Citation:
PMID:  23386286     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The poor viability of transplanted stem cells hampers their therapeutic efficacy for treatment of myocardial infarction. The aim of this study was to investigate whether rosuvastatin improved survival of adipose-derived mesenchymal stem cells (AD-MSCs) after transplantation into infarcted hearts. AD-MSCs isolated from Tg(Fluc-egfp) mice which constitutively express both firefly luciferase (Fluc) and enhanced green fluorescent protein were transplanted into infarcted hearts with or without rosuvastatin administration. Longitudinal in vivo bioluminescence imaging and histological staining revealed that rosuvastatin enhanced the survival of engrafted AD-MSCs. Furthermore, combined therapy of AD-MSC and rosuvastatin reduced fibrosis, decreased cardiomyocyte apoptosis, and preserved heart function. AD-MSCs were then subjected to hypoxia and serum deprivation injury in vitro to mimic the ischemic environment. Rosuvastatin (10(-6) mmol/L) enhanced the viability and paracrine effect of AD-MSCs, and decreased their apoptotic rate. Western blotting revealed that rosuvastatin supplementation increased Akt and ERK phosphorylation, which resulted in FoxO3a phosphorylation and nuclear export. In addition, rosuvastatin administration decreased the pro-apoptotic proteins Bim and Bax, and increased the anti-apoptotic proteins Bcl-xL and Bcl-2. Furthermore, these effects were abolished by PI3K inhibitor LY294002 and MEK1/2 inhibitor U0126. This study demonstrates that rosuvastatin may improve the survival of engrafted AD-MSCs at least in part through the PI3K/Akt and MEK/ERK1/2 signaling pathways. Combination therapy with rosuvastatin and AD-MSCs has a synergetic effect on improving myocardial function after infarction.
Authors:
Zheng Zhang; Shuang Li; Mingliang Cui; Xue Gao; Dongdong Sun; Xing Qin; Kazim Narsinh; Chunhong Li; Hongbing Jia; Congye Li; Yaling Han; Haichang Wang; Feng Cao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-02-06
Journal Detail:
Title:  Basic research in cardiology     Volume:  108     ISSN:  1435-1803     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-06     Completed Date:  2013-07-18     Revised Date:  2014-08-20    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  333     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / cytology
Animals
Apoptosis / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
Combined Modality Therapy
Fluorobenzenes / therapeutic use*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
MAP Kinase Signaling System / physiology*
Male
Mesenchymal Stem Cell Transplantation*
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Myocardial Infarction / metabolism,  therapy*
Myocytes, Cardiac
Phosphatidylinositol 3-Kinases / metabolism*
Phosphorylation / drug effects
Proto-Oncogene Proteins c-akt / metabolism*
Pyrimidines / therapeutic use*
Signal Transduction / drug effects
Sulfonamides / therapeutic use*
Treatment Outcome
Chemical
Reg. No./Substance:
0/Fluorobenzenes; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pyrimidines; 0/Sulfonamides; 287714-41-4/rosuvastatin; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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