TY - JOUR
T1 - Integrating GRK2 and NFkappaB in the Pathophysiology of Cardiac Hypertrophy
AU - Sorriento, Daniela
AU - Santulli, Gaetano
AU - Franco, Antonietta
AU - Cipolletta, Ersilia
AU - Napolitano, Luigi
AU - Gambardella, Jessica
AU - Gomez-Monterrey, Isabel
AU - Campiglia, Pietro
AU - Trimarco, Bruno
AU - Iaccarino, Guido
AU - Ciccarelli, Michele
N1 - Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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.
AB - 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.
KW - ANF
KW - GRK2
KW - Left ventricular hypertrophy
KW - NFκB
UR - http://www.scopus.com/inward/record.url?scp=84947493668&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84947493668&partnerID=8YFLogxK
U2 - 10.1007/s12265-015-9646-0
DO - 10.1007/s12265-015-9646-0
M3 - Article
C2 - 26224342
AN - SCOPUS:84947493668
SN - 1937-5387
VL - 8
SP - 493
EP - 502
JO - Journal of Cardiovascular Translational Research
JF - Journal of Cardiovascular Translational Research
IS - 8
ER -