Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts.
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.
Yang
Yue-Jin
YJ
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.
Qian
Hai-Yan
HY
Huang
Ji
J
Geng
Yong-Jian
YJ
Gao
Run-Lin
RL
Dou
Ke-Fei
KF
Yang
Guo-Sheng
GS
Li
Jian-Jun
JJ
Shen
Rui
R
He
Zuo-Xiang
ZX
Lu
Min-Jie
MJ
Zhao
Shi-Hua
SH
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
D015415:Biomarkers; D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin