Integrating GRK2 and NFkappaB in the Pathophysiology of Cardiac Hypertrophy

Daniela Sorriento, Gaetano Santulli, Antonietta Franco, Ersilia Cipolletta, Luigi Napolitano, Jessica Gambardella, Isabel Gomez-Monterrey, Pietro Campiglia, Bruno Trimarco, Guido Iaccarino, Michele Ciccarelli

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23 Scopus citations

Abstract

G protein coupled receptor kinase type 2 (GRK2) plays an important role in the development and maintenance of cardiac hypertrophy and heart failure even if its exact role is still unknown. In this study, we assessed the effect of GRK2 on the regulation of cardiac hypertrophy. In H9C2 cells, GRK2 overexpression increased atrial natriuretic factor (ANF) activity and enhanced phenylephrine-induced ANF response, and this is associated with an increase of NFκB transcriptional activity. The kinase dead mutant and a synthetic inhibitor of GRK2 activity exerted the opposite effect, suggesting that GRK2 regulates hypertrophy through upregulation of NFκB activity in a phosphorylation-dependent manner. In two different in vivo models of left ventricle hypertrophy (LVH), the selective inhibition of GRK2 activity prevented hypertrophy and reduced NFκB transcription activity. Our results suggest a previously undisclosed role for GRK2 in the regulation of hypertrophic responses and propose GRK2 as potential therapeutic target for limiting LVH.

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Keywords

  • ANF
  • GRK2
  • Left ventricular hypertrophy
  • NFκB

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

Sorriento, D., Santulli, G., Franco, A., Cipolletta, E., Napolitano, L., Gambardella, J., Gomez-Monterrey, I., Campiglia, P., Trimarco, B., Iaccarino, G., & Ciccarelli, M. (2015). Integrating GRK2 and NFkappaB in the Pathophysiology of Cardiac Hypertrophy. Journal of Cardiovascular Translational Research, 8(8), 493-502. https://doi.org/10.1007/s12265-015-9646-0