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|Type:||Artigo de periódico|
|Title:||Focal adhesion kinase governs cardiac concentric hypertrophic growth by activating the AKT and mTOR pathways|
|Author:||Clemente, C. F. M. Z.|
Costa, A. P. Dalla
Consonni, S. R.
Antunes, J. E.
Rocco, S. A.
Pereira, M. B.
Judice, C. C.
Joazeiro, P. P.
Matos-Souza, J. R.
Franchini, K. G.
|Abstract:||The heart responds to sustained overload by hypertrophic growth in which the myocytes distinctly thicken or elongate on increases in systolic or diastolic stress. Though potentially adaptive, hypertrophy itself may predispose to cardiac dysfunction in pathological settings. The mechanisms underlying the diverse morphology and outcomes of hypertrophy are uncertain. Here we used a focal adhesion kinase (FAK) cardiac-specific transgenic mice model (FAK-Tg) to explore the function of this non-receptor tyrosine kinase on the regulation of myocyte growth. FAK-Tg mice displayed a phenocopy of concentric cardiac hypertrophy, reflecting the relative thickening of the individual myocytes. Moreover, FAK-Tg mice showed structural, functional and molecular features of a compensated hypertrophic growth, and preserved responses to chronic pressure overload. Mechanistically, FAK overexpression resulted in enhanced myocardial FAK activity, which was proven by treatment with a selective FAK inhibitor to be required for the cardiac hypertrophy in this model. Our results indicate that upregulation of FAK does not affect the activity of Src/ERK1/2 pathway, but stimulated signaling by a cascade that encompasses PI3K, AKT, mTOR, S6K and rpS6. Moreover, inhibition of the mTOR complex by rapamycin extinguished the cardiac hypertrophy of the transgenic FAK mice. These findings uncover a unique role for FAK in regulating the signaling mechanisms that governs the selective myocyte growth in width, likely controlling the activity of PI3K/AKT/mTOR pathway, and suggest that FAK activation could be important for the adaptive response to increases in cardiac afterload. This article is part of a Special Issue entitled "Local Signaling in Myocytes". (C) 2011 Elsevier Ltd. All rights reserved.|
|Citation:||Journal of Molecular and Cellular Cardiology. Elsevier, v.52, n.2, p.493-501, 2012|
|Appears in Collections:||IB - Artigos e Outros Documentos|
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