| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, United States
2 Moleuclar Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: kxwalsh{at}bu.edu.
To investigate molecular mechanisms involved in the development of cardiac hypertrophy and heart failure, a tetracycline-regulated transgenic system to conditionally switch a constitutively-active form of the Akt1 protein kinase on or off in the adult heart was developed. Short-term activation (2 wk) of Akt1 resulted in completely reversible hypertrophy with maintained contractility. In contrast, chronic Akt1 activation (6 wk) induced extensive cardiac hypertrophy, severe contractile dysfunction and massive interstitial fibrosis. The focus of this study was to create a transcript expression profile of the heart as it undergoes reversible Akt1-mediated hypertrophy and during the transition from compensated hypertrophy to heart failure. Heart tissue was analyzed before transgene induction, 2 wk after transgene induction, 2 wk of transgene induction followed by 2 days of repression, 6 wk after transgene induction and 6 wk of transgene induction followed by 2 wk of repression. Acute overexpression of Akt1 (2 wk) leads to changes in the expression of 826 transcripts relative to non-induced hearts, whereas chronic induction (6 wk) led to changes in the expression of 1611, of which 65% represented transcripts that were regulated during the pathological phase of heart growth. Another set of genes identified were uniquely regulated during heart regression but not growth, indicating that non-overlapping transcription programs participate in the processes of cardiac hypertrophy and atrophy. These data define the gene regulatory programs downstream of Akt that control heart size and contribute to the transition from compensatory hypertrophy to heart failure.
This article has been cited by other articles:
|
|
 |
|
  Y. Oshima, N. Ouchi, K. Sato, Y. Izumiya, D. R. Pimentel, and K. Walsh Follistatin-Like 1 Is an Akt-Regulated Cardioprotective Factor That Is Secreted by the Heart Circulation, June 17, 2008; 117(24): 3099 - 3108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Y. Liu, W.-F. Cai, H.-Z. Yang, B. Cui, Z.-R. Chen, H.-Z. Liu, J. Yan, W. Jin, H.-M. Yan, B.-M. Xin, et al. Bacillus Calmette-Guerin and TLR4 Agonist Prevent Cardiovascular Hypertrophy and Fibrosis by Regulating Immune Microenvironment J. Immunol., June 1, 2008; 180(11): 7349 - 7357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. N. Papanicolaou, Y. Izumiya, and K. Walsh Forkhead Transcription Factors and Cardiovascular Biology Circ. Res., January 4, 2008; 102(1): 16 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-Q. Jin, J. Zhang, Y. Huang, H. E. Hoover, D. A. Vessey, and J. S. Karliner A sphingosine kinase 1 mutation sensitizes the myocardium to ischemia/reperfusion injury Cardiovasc Res, October 1, 2007; 76(1): 41 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Padmasekar, R. Nandigama, M. Wartenberg, K.-D. Schluter, and H. Sauer The acute phase protein {alpha}2-macroglobulin induces rat ventricular cardiomyocyte hypertrophy via ERK1,2 and PI3-kinase/Akt pathways* Cardiovasc Res, July 1, 2007; 75(1): 118 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Shiojima and K. Walsh Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway Genes & Dev., December 15, 2006; 20(24): 3347 - 3365. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
