title: Atorvastatin improves microenvironment to enhance the beneficial effects of BMSCs therapy in a rabbit model of acute myocardial infarction.
abstract: OBJECTIVE
  To investigate the beneficial effects of atorvastatin added to the cell therapy with bone marrow-derived mesenchymal stromal cells (BMSCs) in a rabbit model of acute myocardial infarction (AMI).
  
  
  METHODS
  Rabbits were randomly divided into control group (n=10), bone marrow stem cells transplantation group (n=10), and BMSCs + atorvastatin group (n=10). AMI was established by ligating the left descending coronary artery. The left ventricular (LV) function was evaluated by echocardiography. H&E staining and Masson's Trichrome staining were performed to evaluate inflammatory cell infiltration and cardiac fibrosis. Immunohistochemistry and TUNEL were conducted to assess survival, differentiation, and apoptosis of transplanted cells and cardiomyocytes.
  
  
  RESULTS
  BMSCs decreased LV systolic and diastolic diameters and increased LV ejection fractions, LV fractional shortening, LV systolic pressure and LV end-diastolic pressure. Atorvastatin synergistically enhanced the BMSCs-induced improvements of ischemic cardiac dysfunction. Atorvastatin reduced inflammatory cell infiltration, cardiac fibrosis, and derangement of myocardial morphology/structure. Atorvastatin added a protective effect to cardiomyocytes against apoptotic cell death in infarct and peri-infarct areas, and also increased the survival rate of implanted BMSCs in acute myocardial ischemia. Atorvastatin also promoted cardiac differentiation of implanted BMSCs in infarct myocardium.
  
  
  CONCLUSIONS
  Atorvastatin acts to improve the microenvironment both by synergistically enhancing the existing effects of BMSCs and by adding new therapeutic effects to BMSCs transplantation, and this combinational therapy is a superior cell/pharmacological therapeutic approach that merits future preclinical and clinical studies.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Qu
authors.forename: Hongxin
authors.initials: H
authors.lastname: Xu
authors.forename: Yihao
authors.initials: Y
authors.lastname: Tian
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000628:therapy; D032383:Myocytes, Cardiac / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin