title: Rosuvastatin treatment activates JAK-STAT pathway and increases efficacy of allogeneic mesenchymal stem cell transplantation in infarcted hearts.
abstract: 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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Yue-Jin
authors.initials: YJ
authors.lastname: Yang
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Qian
authors.forename: Yi-Da
authors.initials: YD
authors.lastname: Tang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D058948:Cell Tracking; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000201:enzymology; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000201:enzymology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D000068718:Rosuvastatin Calcium; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors; D014184:Transplantation, Homologous; D020032:Tyrphostins / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D014998:Y Chromosome
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D013449:Sulfonamides; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D000068718:Rosuvastatin Calcium; C507927:Jak2 protein, rat; D053614:Janus Kinase 2