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Focal adhesion kinase signaling in cardiac hypertrophy and failure

Abstract

Focal adhesion kinase (FAK) is a broadly expressed tyrosine kinase implicated in cellular functions such as migration, growth and survival. Emerging data support a role for FAK in cardiac development, reactive hypertrophy and failure. Data reviewed here indicate that FAK plays a critical role at the cellular level in the responses of cardiomyocytes and cardiac fibroblasts to biomechanical stress and to hypertrophic agonists such as angiotensin II and endothelin. The signaling mechanisms regulated by FAK are discussed to provide insight into its role in the pathophysiology of cardiac hypertrophy and failure.

Focal adhesion kinase; Mechanical signaling; Cardiovascular system; Signal transduction


Braz J Med Biol Res, January 2009, Volume 42(1) 44-52

Focal adhesion kinase signaling in cardiac hypertrophy and failure

K.G. Franchini, C.F.M.Z. Clemente and T.M. Marin

Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil

Text

References Correspondence and Footnotes

Abstract

Focal adhesion kinase (FAK) is a broadly expressed tyrosine kinase implicated in cellular functions such as migration, growth and survival. Emerging data support a role for FAK in cardiac development, reactive hypertrophy and failure. Data reviewed here indicate that FAK plays a critical role at the cellular level in the responses of cardiomyocytes and cardiac fibroblasts to biomechanical stress and to hypertrophic agonists such as angiotensin II and endothelin. The signaling mechanisms regulated by FAK are discussed to provide insight into its role in the pathophysiology of cardiac hypertrophy and failure.

Figure 2. Ventricular adult cardiomyocyte fluorescent imaging. A, Anti-focal adhesion kinase (FAK) staining in green. B, Phalloidin staining in red. C, Merge anti-FAK/phalloidin.

Figure 3. Focal adhesion kinase (FAK) depletion impairs the hypertrophic responses of cardiomyocytes to mechanical stress (A, non-stimulated; B, stretched _ 24 h; C, depleted of FAK and stretched cardiomyocyte; bar = 10 µm for panels A-C). D, High magnification (1200X) of anti-FAK myocardial staining (yellowish) from 12-week banded mice highlighting an area of focal myocardial fibrosis. E, Low magnification (400X) of anti-FAK staining from a myocardial biopsy taken from a patient with heart failure due to mitral regurgitation. F, Low magnification (400X) of Masson trichrome staining (green) from 6-week banded mice treated with an irrelevant small interfering RNA (siRNA) targeted to green fluorescent protein. G, Low magnification (400X) of Masson trichrome staining from a 6-week banded mouse treated with siRNA targeted to FAK.

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  • K.G. Franchini, C.F.M.Z. Clemente and T.M. Marin. Focal adhesion kinase signaling in cardiac hypertrophy and failure. Braz J Med Biol Res 2009; 42: 44-52.
  • K.G. Franchini, C.F.M.Z. Clemente and T.M. Marin. Focal adhesion kinase signaling in cardiac hypertrophy and failure. Braz J Med Biol Res 2009; 42: 44-52.
  • Publication Dates

    • Publication in this collection
      12 Feb 2009
    • Date of issue
      Jan 2009

    History

    • Received
      08 July 2008
    • Accepted
      11 Dec 2008
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