| First Author | Scimia MC | Year | 2012 |
| Journal | Nature | Volume | 488 |
| Issue | 7411 | Pages | 394-8 |
| PubMed ID | 22810587 | Mgi Jnum | J:186777 |
| Mgi Id | MGI:5433236 | Doi | 10.1038/nature11263 |
| Citation | Scimia MC, et al. (2012) APJ acts as a dual receptor in cardiac hypertrophy. Nature 488(7411):394-8 |
| abstractText | 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 Galphai 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 Galphai. 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. |
