Published online before print May 13, 2004, doi: 10.1161/01.RES.0000132279.99249.f4
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2004 American Heart Association, Inc.
Integrative Physiology |
Expression of Mutant p193 and p53 Permits Cardiomyocyte Cell Cycle Reentry After Myocardial Infarction in Transgenic Mice
From the Wells Center for Pediatric Research and Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Ind. Present address for S.-C.T. is the Development Center for Biotechnology, Taipei, Taiwan.
Correspondence to Loren J. Field, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 West Walnut St, R4 Building, Rm W376, Indianapolis, IN 46202-5225. E-mail ljfield{at}iupui.edu
Previous studies have demonstrated that expression of p193 and p53 mutants with dominant-interfering activities renders embryonic stem cell–derived cardiomyocytes responsive to the growth promoting activities of the E1A viral oncoproteins. In this study, the effects of p53 and p193 antagonization on cardiomyocyte cell cycle activity in normal and infarcted hearts were examined. Transgenic mice expressing the p193 and/or the p53 dominant-interfering mutants in the heart were generated. Transgene expression had no effect on cardiomyocyte cell cycle activity in uninjured adult hearts. In contrast expression of either transgene resulted in a marked induction of cardiomyocyte cell cycle activity at the infarct border zone at 4 weeks after permanent coronary artery occlusion. Expression of the p193 dominant-interfering mutant was also associated with an induction of cardiomyocyte DNA synthesis in the interventricular septa of infarcted hearts. A concomitant and marked reduction in hypertrophic cardiomyocyte growth was observed in the septa of hearts expressing the p193 dominant-interfering transgene, suggesting that cell cycle activation might partially counteract the adverse ventricular remodeling that occurs after infarction. Collectively these data suggest that antagonization of p193 and p53 activity relaxes the otherwise stringent regulation of cardiomyocyte cell cycle reentry in the injured adult heart.
Key Words: cardiomyocyte proliferation • apoptosis • DNA synthesis • heart regeneration
This article has been cited by other articles:
 |
|
 |
|
  R J Hassink, H Nakajima, H O Nakajima, P A Doevendans, and L J Field Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction Heart, July 15, 2009; 95(14): 1159 - 1164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhu, M. H. Soonpaa, H. Chen, W. Shen, R. M. Payne, E. A. Liechty, R. L. Caldwell, W. Shou, and L. J. Field Acute Doxorubicin Cardiotoxicity Is Associated With p53-Induced Inhibition of the Mammalian Target of Rapamycin Pathway Circulation, January 6, 2009; 119(1): 99 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lorts, J. A. Schwanekamp, J. W. Elrod, M. A. Sargent, and J. D. Molkentin Genetic Manipulation of Periostin Expression in the Heart Does Not Affect Myocyte Content, Cell Cycle Activity, or Cardiac Repair Circ. Res., January 2, 2009; 104(1): e1 - e7. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tamamori-Adachi, H. Takagi, K. Hashimoto, K. Goto, T. Hidaka, U. Koshimizu, K. Yamada, I. Goto, Y. Maejima, M. Isobe, et al. Cardiomyocyte proliferation and protection against post-myocardial infarction heart failure by cyclin D1 and Skp2 ubiquitin ligase Cardiovasc Res, November 1, 2008; 80(2): 181 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ebelt, Y. Zhang, A. Kampke, J. Xu, A. Schlitt, M. Buerke, U. Muller-Werdan, K. Werdan, and T. Braun E2F2 expression induces proliferation of terminally differentiated cardiomyocytes in vivo Cardiovasc Res, November 1, 2008; 80(2): 219 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Crisostomo, A. M. Abarbanell, M. Wang, T. Lahm, Y. Wang, and D. R. Meldrum Embryonic stem cells attenuate myocardial dysfunction and inflammation after surgical global ischemia via paracrine actions Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1726 - H1735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Hassink, K. B. Pasumarthi, H. Nakajima, M. Rubart, M. H. Soonpaa, A. B. de la Riviere, P. A. Doevendans, and L. J. Field Cardiomyocyte cell cycle activation improves cardiac function after myocardial infarction Cardiovasc Res, April 1, 2008; 78(1): 18 - 25. [Abstract] [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]
|
|
|
|
|
|
L. W. van Laake, S. van den Driesche, S. Post, A. Feijen, M. A. Jansen, M. H. Driessens, J. J. Mager, R. J. Snijder, C. J. J. Westermann, P. A. Doevendans, et al. Endoglin Has a Crucial Role in Blood Cell-Mediated Vascular Repair Circulation, November 21, 2006; 114(21): 2288 - 2297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsusaka, T. Ide, S. Matsushima, M. Ikeuchi, T. Kubota, K. Sunagawa, S. Kinugawa, and H. Tsutsui Targeted deletion of p53 prevents cardiac rupture after myocardial infarction in mice Cardiovasc Res, June 1, 2006; 70(3): 457 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Nakajima, H. O. Nakajima, K. Dembowsky, K. B.S. Pasumarthi, and L. J. Field Cardiomyocyte Cell Cycle Activation Ameliorates Fibrosis in the Atrium Circ. Res., January 6, 2006; 98(1): 141 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Regula and L. A. Kirshenbaum Breaking Down Cell-Cycle Barriers in the Adult Heart Circ. Res., June 25, 2004; 94(12): 1524 - 1526. [Full Text] [PDF]
|
|