APJ acts as a dual receptor in cardiac hypertrophy.

Journal: 
Nature
Publication Year: 
2012
Authors: 
Maria Cecilia Scimia , Cecilia Hurtado , Saugata Ray , Scott Metzler , Ke Wei , Jianming Wang , Chris E Woods , Nicole H Purcell , Daniele Catalucci , Takashi Akasaka , Orlando F Bueno , George P Vlasuk , Perla Kaliman , Rolf Bodmer , Layton H Smith , Euan Ashley , Mark Mercola , Joan Heller Brown , Pilar Ruiz-Lozano
Public Summary: 
Scientific Abstract: 
Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues. Here we report that genetic loss of APJ, a G-protein-coupled receptor, confers resistance to chronic pressure overload by markedly reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin-independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to stretch, indicating that APJ is a mechanosensor. Activation of APJ by stretch increases cardiomyocyte cell size and induces molecular markers of hypertrophy. Whereas apelin stimulates APJ to activate Galpha(i) and elicits a protective response, stretch signals in an APJ-dependent, G-protein-independent fashion to induce hypertrophy. Stretch-mediated hypertrophy is prevented by knockdown of beta-arrestins or by pharmacological doses of apelin acting through Galpha(i). Taken together, our data indicate that APJ is a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin. By sensing the balance between these stimuli, APJ occupies a pivotal point linking sustained overload to cardiomyocyte hypertrophy.

© 2013 California Institute for Regenerative Medicine