Cai Anping, Qiu Ruofeng, Li Liwen, Zheng Dongdan, Dong Yugang, Yu Danqing, Huang Yuli, Rao Shaoqi, Zhou Yingling, Mai Weiyi
Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China ; Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
PLoS One. 2013 Dec 2;8(12):e79100. doi: 10.1371/journal.pone.0079100. eCollection 2013.
Adipose-derived mesenchymal stem cells (ASCs) transplantation is a promising approach for myocardium repair. Promotion of ASCs migration and survival is the key for improving ASCs efficiency. SDF-1α is a critical factor responsible for ASCs migration and survival. Atorvastatin (Ator) is capable of up-regulating SDF-1α. Therefore, we're going to investigate whether ASCs migration and survival could be improved with atorvastatin.
In vitro study, cardiomyocytes were subjected to anoxia-reoxygenation injury and subsequently divided into different groups: group blank control, Ator, Ator plus L-NAME (A+L-NAME) and Ator plus AMD3100 (A+AMD3100).When migration analysis completed, cardiomyocytes were used for subsequent analyses. In vivo study, rats underwent ischemia-reperfusion injury were assigned into different groups corresponding to in vitro protocols. ASCs were transplanted on the seventh day of atorvastatin therapy. Seven days later, the rates of migration, differentiation and apoptosis were evaluated.
Compared with other groups, ASCs migration in vitro was significantly improved in group Ator, which was dependent on SDF-1α/CXCR-4 coupling. Results of in vivo study were consistent with that of in vitro study, further supporting the notion that the efficacy of atorvastatin on ASCs migration improvement was related to SDF-1α/CXCR-4 axis. Higher vessel density in group Ator might be another mechanism responsible for migration improvement. Concomitantly, apoptosis was significantly reduced in group Ator, whereas no significant difference of differentiation was found.
Migration and survival of ASCs could be improved by atorvastatin under ischemia-reperfusion injury, which were ascribed to SDF-1α/CXCR-4 axis.
脂肪间充质干细胞（ASCs）移植是一种有前景的心肌修复方法。促进ASCs迁移和存活是提高ASCs疗效的关键。基质细胞衍生因子-1α（SDF-1α）是负责ASCs迁移和存活的关键因素。阿托伐他汀（Ator）能够上调SDF-1α。因此，我们将研究阿托伐他汀是否能改善ASCs的迁移和存活。
体外研究中，心肌细胞经历缺氧-复氧损伤，随后分为不同组：空白对照组、阿托伐他汀组、阿托伐他汀加L- NAME组（A + L-NAME）和阿托伐他汀加AMD3100组（A + AMD3100）。迁移分析完成后，心肌细胞用于后续分析。体内研究中，经历缺血-再灌注损伤的大鼠被分为与体外实验方案相对应的不同组。在阿托伐他汀治疗的第7天移植ASCs。7天后，评估迁移、分化和凋亡率。
与其他组相比，阿托伐他汀组体外ASCs迁移显著改善，这依赖于SDF-1α/CXCR-4偶联。体内研究结果与体外研究结果一致，进一步支持了阿托伐他汀改善ASCs迁移的疗效与SDF-1α/CXCR-4轴相关的观点。阿托伐他汀组较高的血管密度可能是迁移改善的另一个机制。同时，阿托伐他汀组凋亡显著减少，而分化未发现显著差异。
在缺血-再灌注损伤情况下，阿托伐他汀可改善ASCs的迁移和存活，这归因于SDF-1α/CXCR-4轴。
