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Citations to this article

Regulation of cardiac hypertrophy in vivo by the stress-activated protein kinases/c-Jun NH2-terminal kinases
Gabriel Choukroun, … , Anthony Rosenzweig, Thomas Force
Gabriel Choukroun, … , Anthony Rosenzweig, Thomas Force
Published August 15, 1999
Citation Information: J Clin Invest. 1999;104(4):391-398. https://doi.org/10.1172/JCI6350.
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Article

Regulation of cardiac hypertrophy in vivo by the stress-activated protein kinases/c-Jun NH2-terminal kinases

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Abstract

Cardiac hypertrophy often presages the development of heart failure. Numerous cytosolic signaling pathways have been implicated in the hypertrophic response in cardiomyocytes in culture, but their roles in the hypertrophic response to physiologically relevant stimuli in vivo is unclear. We previously reported that adenovirus-mediated gene transfer of SEK-1(KR), a dominant inhibitory mutant of the immediate upstream activator of the stress-activated protein kinases (SAPKs), abrogates the hypertrophic response of neonatal rat cardiomyocytes to endothelin-1 in culture. We now report that gene transfer of SEK-1(KR) to the adult rat heart blocks SAPK activation by pressure overload, demonstrating that the activity of cytosolic signaling pathways can be inhibited by gene transfer of loss-of-function mutants in vivo. Furthermore, gene transfer of SEK-1(KR) inhibited pressure overload–induced cardiac hypertrophy, as determined by echocardiography and several postmortem measures including left ventricular (LV) wall thickness, the ratio of LV weight to body weight, cardiomyocyte diameter, and inhibition of atrial natriuretic factor expression. Our data suggest that the SAPKs are critical regulators of cardiac hypertrophy in vivo, and therefore may serve as novel drug targets in the treatment of hypertrophy and heart failure.

Authors

Gabriel Choukroun, Roger Hajjar, Stefanie Fry, Federica del Monte, Syed Haq, J. Luis Guerrero, Michael Picard, Anthony Rosenzweig, Thomas Force

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Journal of Molecular and Cellular Cardiology 2000
Glycogen Synthase Kinase-3  Is a Negative Regulator of Cardiomyocyte Hypertrophy
S Haq, G Choukroun, ZB Kang, H Ranu, T Matsui, A Rosenzweig, JD Molkentin, A Alessandrini, J Woodgett, R Hajjar, A Michael, T Force
The Journal of Cell Biology 2000
Calcineurin Promotes Protein Kinase C and c-Jun NH 2 -terminal Kinase Activation in the Heart: CROSS-TALK BETWEEN CARDIAC HYPERTROPHIC SIGNALING PATHWAYS
LJ de Windt, HW Lim, S Haq, T Force, JD Molkentin
The Journal of biological chemistry 2000
The Akt-Glycogen Synthase Kinase 3β Pathway Regulates Transcription of Atrial Natriuretic Factor Induced by β-Adrenergic Receptor Stimulation in Cardiac Myocytes
C Morisco, D Zebrowski, G Condorelli, P Tsichlis, SF Vatner, J Sadoshima
The Journal of biological chemistry 2000
Integrin signaling's potential for mediating gene expression in hypertrophying skeletal muscle
JA Carson, L Wei
Journal of applied physiology 2000
Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement
C Fink, S Ergün, D Kralisch, U Remmers, J Weil, T Eschenhagen
The FASEB Journal 2000
Prospects for Gene Therapy for Heart Failure
RJ Hajjar, F del Monte, T Matsui, A Rosenzweig
Circulation research 2000
Calcineurin and Beyond: Cardiac Hypertrophic Signaling
JD Molkentin
Circulation research 2000
Important Role of Angiotensin II–Mediated c-Jun NH 2 -Terminal Kinase Activation in Cardiac Hypertrophy in Hypertensive Rats
Y Izumi, S Kim, Y Zhan, M Namba, H Yasumoto, H Iwao
Hypertension 2000
Molecular Approaches to Heart Failure Therapy
G Hasenfuss, E Marbán
2000
Signaling pathways mediating the response to hypertrophic stress in the heart
T Force, R Hajjar, FD Monte, A Rosenzweig, G Choukroun
Gene expression 1999

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