doi: 10.1161/CIRCRESAHA.107.165621
© 2007 American Heart Association, Inc.
Editorials |
Not All Hypertrophy Is Created Equal
From the Cardiac Muscle Research Laboratory (R.L.), Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; and the Center for Translational Medicine (T.F.), Jefferson Medical College, Philadelphia, Pa.
Correspondence to Dr Ronglih Liao, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 431, Boston, MA 02115. E-mail rliao@rics.bwh.harvard.edu; and Dr Thomas Force, Center for Translational Medicine, Jefferson Medical College, 1025 Walnut St, room 316, Philadelphia, PA 19107. E-mail thomas.force@jefferson.edu
See related article, pages 1164–1174
Key Words: cardiac hypertrophy • heart failure • glycogen synthase kinase-3ß • therapeutic target
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Cardiac hypertrophy is the natural response of myocardium to various stressors, including neurohormonal stimuli, hemodynamic overload, and injury. In the face of continued stress, pathological hypertrophy progresses to a loss of cardiomyocytes, the development of fibrosis, and, ultimately, heart failure. Emerging evidence has shown that glycogen synthase kinase-3ß (GSK-3ß) is an important negative regulator of cardiomyocyte hypertrophy, yet inhibition of GSK-3ß has been shown to reduce cell death after ischemia reperfusion. Therefore, it has been difficult to predict what the consequences of chronic inhibition of GSK-3 in the heart would be because it might be a balance between the potential for the aggravation of cardiac hypertrophy versus antiapoptotic effects. In this issue of Circulation Research, Hirotani and colleagues report that sustained inhibition of GSK-3ß in postneonatal hearts results in well-compensated "physiologic" cardiac hypertrophy and, most intriguingly, exerts protective effects against the development of "pathological" hypertrophy and heart failure with pressure overload.1 Although there are a number of concerns that need to be addressed before targeting GSK-3 for the treatment of heart failure, this "best of both worlds" outcome provides an interesting and favorable rationale for such intervention.
The GSK-3 family of protein kinases is encoded by 2 genes, 
and ß. They are highly conserved throughout evolution and are critical to the regulation of diverse biological processes ranging from organ development to cell death, including cell growth, cell cycling, cytoskeletal organization, and metabolism.2,3 Furthermore, dysregulation of GSK-3ß has been implicated in the pathogenesis of many human diseases including Alzheimer disease,
Related Article:
Circ. Res. 2007 101: 1164-1174.
This article has been cited by other articles:
 |
|
 |
|
  A. Darmellah, C. Rucker-Martin, and D. Feuvray ERM proteins mediate the effects of Na+/H+ exchanger (NHE1) activation in cardiac myocytes Cardiovasc Res, February 1, 2009; 81(2): 294 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Endoh Novel signalling cascade for cardiac hypertrophy activation by uncoupling and internalization of {beta}1-adrenoceptors Cardiovasc Res, April 1, 2008; 78(1): 5 - 7. [Full Text] [PDF]
|
|