APJ acts as a dual receptor in cardiac hypertrophy

Maria Cecilia Scimia, Cecilia Hurtado, Saugata Ray, Scott Metzler, Ke Wei, Jianming Wang, Chris E. Woods, Nicole H. Purcell, Daniele Catalucci, Takeshi Akasaka, Orlando F. Bueno, George P. Vlasuk, Perla Kaliman, Rolf Bodmer, Layton H. Smith, Euan Ashley, Mark Mercola, Joan Heller Brown, Pilar Ruiz-Lozano

Research output: Contribution to journalArticlepeer-review


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 Gα 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 β-arrestins or by pharmacological doses of apelin acting through Gα 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.

Original languageEnglish
Pages (from-to)394-398
Number of pages5
Issue number7411
Publication statusPublished - Aug 16 2012

ASJC Scopus subject areas

  • General


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