Cheng Richard K, Asai Tomohiro, Tang Haiying, Dashoush Nurin H, Kara Rina J, Costa Kevin D, Naka Yoshifumi, Wu Ed X, Wolgemuth Debra J, Chaudhry Hina W
Department of Medicine, Columbia University, New York, NY 10032, USA.
Circ Res. 2007 Jun 22;100(12):1741-8. doi: 10.1161/CIRCRESAHA.107.153544. Epub 2007 May 10.
Mammalian myocardial infarction is typically followed by scar formation with eventual ventricular dilation and heart failure. Here we present a novel model system in which mice constitutively expressing cyclin A2 in the myocardium elicit a regenerative response after infarction and exhibit significantly limited ventricular dilation with sustained and remarkably enhanced cardiac function. New cardiomyocyte formation was noted in the infarcted zones as well as cell cycle reentry of periinfarct myocardium with an increase in DNA synthesis and mitotic indices. The enhanced cardiac function was serially assessed over time by MRI. Furthermore, the constitutive expression of cyclin A2 appears to augment endogenous regenerative mechanisms via induction of side population cells with enhanced proliferative capacity. The ability of cultured transgenic cardiomyocytes to undergo cytokinesis provides mechanistic support for the regenerative capacity of cyclin A2.
哺乳动物心肌梗死后通常会形成瘢痕，最终导致心室扩张和心力衰竭。在此，我们展示了一种新型模型系统，在该系统中，心肌中组成型表达细胞周期蛋白A2的小鼠在梗死后引发再生反应，心室扩张明显受限，心脏功能持续且显著增强。在梗死区域发现了新的心肌细胞形成，以及梗死周围心肌的细胞周期重新进入，DNA合成和有丝分裂指数增加。通过MRI随时间连续评估心脏功能的增强情况。此外，细胞周期蛋白A2的组成型表达似乎通过诱导具有增强增殖能力的侧群细胞来增强内源性再生机制。培养的转基因心肌细胞进行胞质分裂的能力为细胞周期蛋白A2的再生能力提供了机制支持。
