Published online before print May 10, 2007, doi: 10.1161/CIRCRESAHA.107.153544
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on November 19, 2006
Revised on April 20, 2007
Accepted on April 30, 2007
Cyclin A2 Induces Cardiac Regeneration After Myocardial Infarction and Prevents Heart Failure
Richard K. Cheng ;
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.
* To whom correspondence should be addressed. 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
This article has been cited by other articles:
 |
|
 |
|
  C. Stamm, Y.-H. Choi, B. Nasseri, and R. Hetzer A heart full of stem cells: the spectrum of myocardial progenitor cells in the postnatal heart Therapeutic Advances in Cardiovascular Disease, June 1, 2009; 3(3): 215 - 229. [Abstract] [PDF]
|
|
|
|
 |
|
 R. L Kao, W. Browder, and C. Li Cellular Cardiomyoplasty: What Have We Learned? Asian Cardiovasc Thorac Ann, January 1, 2009; 17(1): 89 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Gorr and A. Deten Manipulating myocyte cell cycle control for cardiac repair Cardiovasc Res, November 1, 2008; 80(2): 161 - 162. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Karpurapu, D. Wang, N. K. Singh, Q. Li, and G. N. Rao NFATc1 Targets Cyclin A in the Regulation of Vascular Smooth Muscle Cell Multiplication during Restenosis J. Biol. Chem., September 26, 2008; 283(39): 26577 - 26590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Qiu, H. Dai, K. Jain, R. Shah, C. Hong, J. Pain, B. Tian, D. E. Vatner, S. F. Vatner, and C. Depre Characterization of a Novel Cardiac Isoform of the Cell Cycle-related Kinase That Is Regulated during Heart Failure J. Biol. Chem., August 8, 2008; 283(32): 22157 - 22165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D.T. Costa Divide to survive: myocardial regeneration and functional recovery after cell cycle activation in injured hearts Cardiovasc Res, April 1, 2008; 78(1): 1 - 2. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Li, N. Naqvi, E. Yahiro, K. Liu, P. C. Powell, W. E. Bradley, D. I.K. Martin, R. M. Graham, L. J. Dell'Italia, and A. Husain c-kit Is Required for Cardiomyocyte Terminal Differentiation Circ. Res., March 28, 2008; 102(6): 677 - 685. [Abstract] [Full Text] [PDF]
|
|