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European Heart Journal Advance Access published online on May 2, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn167
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts

Yue-Jin Yang1,*, Hai-Yan Qian1, Ji Huang2, Yong-Jian Geng3, Run-Lin Gao1, Ke-Fei Dou1, Guo-Sheng Yang1, Jian-Jun Li1, Rui Shen4, Zuo-Xiang He4, Min-Jie Lu5 and Shi-Hua Zhao5

1 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
2 Emergency Center of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital University of Medical Sciences & Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, People's Republic of China
3 The Center for Cardiovascular Biology and Atherosclerosis, Department of Internal Medicine, The University of Texas, Health Science Center at Houston, Medical School, Texas Heart Institute, Houston, TX, USA
4 Department of Nuclear Medicine, Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China
5 Department of Radiology, Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China

Received 21 August 2007; revised 12 March 2008; accepted 4 April 2008.

* Corresponding author. Tel: +86 10 88398760, Fax: +86 10 68351786, Email: dr_yuejinyang{at}yahoo.com.cn

Aims: 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.

Methods and 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.

Conclusion: 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.

Key Words: Mesenchymal stem cells • Acute myocardial infarction • Transplantation • Atorvastatin


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