title: Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction.
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 × 10(6) co-ASCs/100 μl phosphate-buffered saline (PBS), 1×10(6) ASCs/100 μl PBS, or 100 μl 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-α, 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.
authors: Department of Cardiology,  The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080,  China.
authors: Anping
authors: A
authors: Cai
authors: Dongdan
authors: D
authors: Zheng
authors: Yugang
authors: Y
authors: Dong
authors: Ruofeng
authors: R
authors: Qiu
authors: Yuli
authors: Y
authors: Huang
authors: Yuanbin
authors: Y
authors: Song
authors: Zhigao
authors: Z
authors: Jiang
authors: Shaoqi
authors: S
authors: Rao
authors: Xinxue
authors: X
authors: Liao
authors: Jian
authors: J
authors: Kuang
authors: Gang
authors: G
authors: Dai
authors: Weiyi
authors: W
authors: Mai
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000637:transplantation; D000818:Animals; D000069059:Atorvastatin; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D050991:GATA4 Transcription Factor / Q000378:metabolism; D006334:Heart Function Tests; D006538:Heptanoic Acids / Q000494:pharmacology*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019210:Troponin I / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
chemical_list: D050991:GATA4 Transcription Factor; D006538:Heptanoic Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D051028:bcl-2-Associated X Protein; D000069059:Atorvastatin