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Integrating GRK2 and NFkappaB in the Pathophysiology of Cardiac Hypertrophy.

Authors: Sorriento, D  Santulli, G  Franco, A  Cipolletta, E  Napolitano, L  Gambardella, J  Gomez-Monterrey, I  Campiglia, P  Trimarco, B  Iaccarino, G  Ciccarelli, M 
Citation: Sorriento D, etal., J Cardiovasc Transl Res. 2015 Nov;8(8):493-502. doi: 10.1007/s12265-015-9646-0. Epub 2015 Jul 30.
Pubmed: (View Article at PubMed) PMID:26224342
DOI: Full-text: DOI:10.1007/s12265-015-9646-0

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 NFkappaB 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 NFkappaB 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 NFkappaB 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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CRRD Object Information
CRRD ID: 11534182
Created: 2016-09-14
Species: All species
Last Modified: 2016-09-14
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.