Vol43 No.11: 857-866

Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction

Anping Cai^1†, Dongdan Zheng^1†, Yugang Dong¹, Ruofeng Qiu¹, Yuli Huang¹, Yuanbin Song¹, Zhigao Jiang¹, Shaoqi Rao², Xinxue Liao¹, Jian Kuang¹, Gang Dai¹, and Weiyi Mai^1*

(1 Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; 2 Department of Epidemiology and Health Statistics, Sun Yat-sen University, Guangzhou 510080, China)

Abstract
����Mesenchymal stem cells (MSCs) have been extensively applied for the restoration of cardiomyocytes loss after acute myocardial infarction (AMI). However, the optimal therapeutic efficacy of MSCs in ischemic heart diseases has been hampered by their poor survival and low differentiated rates. Therefore, the improvement of MSC survival and differentiated rates is warranted and critical for the efficacy of MSCs in AMI. In this paper, MSCs isolated from rat inguinal fat tissues were termed as adipose-derived mesenchymal stem cells (ASCs), and the fourth passage of ASCs was pre-specified by co-culturing with cardiomyocytes in a transwell system termed as co-ASCs. Fourteen days later, GATA-4 (a transcription factor) and cardiac troponin-I were detected by cellular immunofluorescence. Atorvastatin (Ator group) or vehicle (control group) was administrated for the first 24 h after AMI production in rats. Fourteen days later, inflammatory parameters and cardiac function were evaluated. The other surviving rats were injected with a total of 1 �� 106 co-ASCs/100 ��l phosphate-buffered saline (PBS), 1��106 ASCs/100 ��l PBS, or 100 ��l PBS. Twenty-eight days after cell injection, survival and differentiated rates of transplanted cells and cardiac function were evaluated. The percentage of GATA-4 expression in co-ASCs was 28.5% �� 5.6% and of cardiac troponin-I was 22.8% �� 3.2%. Compared with the control group, the number of infiltrating inflammatory cells, myeloperoxidase activity, inflammatory cytokines (VCAM-1, TNF-��, Hs-CRP) mRNA expression, and Bax protein expression were significantly reduced in the three Ator groups, accompanied by a significant improvement of Bcl-2 protein expression and cardiac function (P< 0.05). Compared with the Ator2 + ASCs group and Con + co-ASCs group, the number of 4-6-diamidino-2-phenylindole-stained cells and cardiac troponin-I-positive transplanted cells, concomitant with cardiac function, were improved most prominently in the Ator3 + co-ASCs group (P< 0.05). Pre-amelioration of the cardiac milieu, in conjunction with pre-specification of ASCs, was beneficial for enhancing ASCs' therapeutic efficacy on cardiac function after AMI.

Received: 2011-6-18����Accepted: 2011-7-21

†These authors contributed equally to this work.

*Corresponding author . Tel: +86-20-87755766-8164; Fax: +86-20-87755766-8756; E-mail: [email protected]

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