|Rosuvastatin treatment activates JAK-STAT pathway and increases efficacy of allogeneic mesenchymal stem cell transplantation in infarcted hearts.|
|PMID: 21502705 Owner: NLM Status: MEDLINE|
|BACKGROUND: Widespread death of implanted cells hampers the development of stem cell therapy for acute myocardial infarction (AMI). Our previous studies indicated that statins can protect implanted mesenchymal stem cells (MSCs) against the post-infarct microenvironment, thus increasing the therapeutic effect. However, the underlying mechanisms are unclear. The JAK-STAT pathway participates in regulation of stress responses of the myocardium to various insults. This study aimed to detect whether rosuvastatin (ROSU) facilitates the survival, engraftment, and differentiation of allogeneic bone marrow-derived MSCs in the post-infarct heart via the JAK-STAT signaling pathway.
METHODS AND RESULTS: Female Sprague-Dawley rats were randomized into 5 groups: AMI (control), ROSU gavage (group R), MSCs transplantation (group M), MSCs and ROSU (group M+R), or MSCs, ROSU and a JAK2 inhibitor AG-490 (group M+R+AG). MSCs from male rats were injected into the myocardium 1 week after AMI. Cardiac function and histology, as well as the expression of Y-chromosomal genes and JAK-STAT signaling proteins, were examined at 4 weeks after transplantation. Better functional recovery, increased survival and differentiation of MSCs occurred in group M+R. Furthermore, phosphorylation of JAK2 and STAT3 was higher in group M+R. The effects of ROSU, as well as of activated JAK-STAT proteins, could be attenuated by AG-490.
CONCLUSIONS: ROSU treatment improves the efficacy of stem cell transplantation in infarcted hearts by activation of the JAK2-STAT3 signaling pathway.
|Hui Xu; Yue-Jin Yang; Hai-Yan Qian; Yi-Da Tang; Hong Wang; Qian Zhang|
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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-04-19|
|Title: Circulation journal : official journal of the Japanese Circulation Society Volume: 75 ISSN: 1347-4820 ISO Abbreviation: Circ. J. Publication Date: 2011|
|Created Date: 2011-05-26 Completed Date: 2011-09-16 Revised Date: 2012-06-05|
Medline Journal Info:
|Nlm Unique ID: 101137683 Medline TA: Circ J Country: Japan|
|Languages: eng Pagination: 1476-85 Citation Subset: IM|
|Center for Coronary Heart Disease, Department of Cardiology, Cardiovascular Institute and Fuwai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, PR China.|
|APA/MLA Format Download EndNote Download BibTex|
Cell Differentiation / drug effects
Cell Survival / drug effects
Disease Models, Animal
Fluorobenzenes / pharmacology*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Janus Kinase 2 / antagonists & inhibitors, metabolism*
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells / drug effects*, enzymology
Myocardial Contraction / drug effects
Myocardial Infarction / drug therapy*, enzymology*, physiopathology, surgery*
Myocardium / enzymology
Protein Kinase Inhibitors / pharmacology
Pyrimidines / pharmacology*
Recovery of Function
STAT3 Transcription Factor / metabolism*
Signal Transduction / drug effects*
Stroke Volume / drug effects
Sulfonamides / pharmacology*
Tyrphostins / pharmacology
Ventricular Function, Left / drug effects
|0/Fluorobenzenes; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Protein Kinase Inhibitors; 0/Pyrimidines; 0/STAT3 Transcription Factor; 0/Stat3 protein, rat; 0/Sulfonamides; 0/Tyrphostins; 0/alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; 287714-41-4/rosuvastatin; EC 220.127.116.11/Janus Kinase 2; EC 18.104.22.168/Jak2 protein, rat|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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