Atorvastatin treatment of rats with ischemia-reperfusion injury improves adipose-derived mesenchymal stem cell migration and survival via the SDF-1α/CXCR-4 axis

PLoS One. 2013 Dec 2;8(12):e79100. doi: 10.1371/journal.pone.0079100. eCollection 2013.

Abstract

Background: Adipose-derived mesenchymal stem cells (ASCs) transplantation is a promising approach for myocardium repair. Promotion of ASCs migration and survival is the key for improving ASCs efficiency. SDF-1α is a critical factor responsible for ASCs migration and survival. Atorvastatin (Ator) is capable of up-regulating SDF-1α. Therefore, we're going to investigate whether ASCs migration and survival could be improved with atorvastatin.

Methods: In vitro study, cardiomyocytes were subjected to anoxia-reoxygenation injury and subsequently divided into different groups: group blank control, Ator, Ator plus L-NAME (A+L-NAME) and Ator plus AMD3100 (A+AMD3100).When migration analysis completed, cardiomyocytes were used for subsequent analyses. In vivo study, rats underwent ischemia-reperfusion injury were assigned into different groups corresponding to in vitro protocols. ASCs were transplanted on the seventh day of atorvastatin therapy. Seven days later, the rates of migration, differentiation and apoptosis were evaluated.

Results: Compared with other groups, ASCs migration in vitro was significantly improved in group Ator, which was dependent on SDF-1α/CXCR-4 coupling. Results of in vivo study were consistent with that of in vitro study, further supporting the notion that the efficacy of atorvastatin on ASCs migration improvement was related to SDF-1α/CXCR-4 axis. Higher vessel density in group Ator might be another mechanism responsible for migration improvement. Concomitantly, apoptosis was significantly reduced in group Ator, whereas no significant difference of differentiation was found.

Conclusion: Migration and survival of ASCs could be improved by atorvastatin under ischemia-reperfusion injury, which were ascribed to SDF-1α/CXCR-4 axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology
  • Allografts
  • Animals
  • Atorvastatin
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Chemokine CXCL12 / metabolism*
  • Heptanoic Acids / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Myocardial Reperfusion Injury* / metabolism
  • Myocardial Reperfusion Injury* / pathology
  • Myocardial Reperfusion Injury* / therapy
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, CXCR4 / metabolism*

Substances

  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Cxcr4 protein, rat
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Receptors, CXCR4
  • Atorvastatin

Grants and funding

This work was supported by the grants from the Technology Project Foundation of Guangdong Province, China (2009A030301004, 2011B031800021, and2011B031800263). The research grant of cardiovascular medication of Guangdong Province (2011X25. Medical Scientific Research Grant of the Health Ministry of Guangdong province, China (B2011310, A2012663). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.