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(Circulation Research. 2007;100:1741.)
© 2007 American Heart Association, Inc.

Integrative Physiology

Cyclin A2 Induces Cardiac Regeneration After Myocardial Infarction and Prevents Heart Failure

Richard K. Cheng^*, Tomohiro Asai^*, Haiying Tang, Nurin H. Dashoush, Rina J. Kara, Kevin D. Costa, Yoshifumi Naka, Ed X. Wu, Debra J. Wolgemuth, Hina W. Chaudhry

From the Departments of Medicine (R.K.C., N.H.D., R.K., H.W.C.), Surgery (T.A., Y.N.), Radiology (H.T.), Biomedical Engineering (K.D.C.), and Genetics and Development (D.J.W.), Columbia University, New York; and the Department of Electrical and Electronics Engineering (E.X.W.), University of Hong Kong, China.

Correspondence Hina W. Chaudhry, Department of Medicine, Columbia University College of Physicians & Surgeons, 622 West 168th Street, PH3-342, New York, NY 10032. E-mail hwc7{at}columbia.edu

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.

Key Words: cyclin A2 • cardiac regeneration • side-population cells • heart failure • cell cycle

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