title: Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts.
abstract: OBJECTIVE
  To investigate whether Atorvastatin (Ator) treatment improves the cardiac micro-environment that facilitates survival and differentiation of bone-marrow-derived mesenchymal stem cells (MSCs) implanted in the post-infarct myocardium.
  
  
  RESULTS
  Myocardial infarction was created by coronary ligation and immediately after reperfusion, autologous bone-marrow-derived MSCs were transplanted into the hearts of Chinese swine that were pretreated with or without Ator. Six weeks after transplantation, as evaluated by SPECT and MRI all the animals with Ator showed improved cardiac perfusion and contractility when compared with untreated. Increased survival and differentiation of implanted MSCs and decreased infarct area were observed in the Ator-treated, MSC-implanted animals. In the absence of Ator, MSC transplantation only achieved a modest improvement in perfusion and morphology. The combined treatment with Ator and MSCs significantly inhibited cardiac cell apoptosis, reduced oxidative stress, and suppressed expression of the inflammatory cytokines in the post-infarct myocardium.
  
  
  CONCLUSIONS
  Ator treatment may protect the myocardium undergoing acute infarction and reperfusion by creating a better environment for the survival and differentiation of implanted MSCs. The benefit of the Ator/stem cell combined therapy may result from the statin-mediated inhibition of apoptosis, oxidative stress, and inflammation in the infarcted myocardium.
authors.affiliation: Department of Cardiology, Fu Wai Hospital and Cardiovascular Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, 167 BeiLiShi Rd, Beijing 100037, People's Republic of China.
authors.forename: Yue-Jin
authors.initials: YJ
authors.lastname: Yang
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Qian
authors.forename: Ji
authors.initials: J
authors.lastname: Huang
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Geng
authors.forename: Run-Lin
authors.initials: RL
authors.lastname: Gao
authors.forename: Ke-Fei
authors.initials: KF
authors.lastname: Dou
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Yang
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Shen
authors.forename: Zuo-Xiang
authors.initials: ZX
authors.lastname: He
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Lu
authors.forename: Shi-Hua
authors.initials: SH
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D003131:Combined Modality Therapy / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018810:Magnetic Resonance Angiography; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D018384:Oxidative Stress / Q000502:physiology; D011758:Pyrroles / Q000627:therapeutic use*; D015996:Survival Rate; D013552:Swine; D013556:Swine, Miniature; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin