학술논문
APJ acts as a dual receptor in cardiac hypertrophy.
Document Type
Article
Author
Scimia, Maria Cecilia; Hurtado, Cecilia; Ray, Saugata; Metzler, Scott; Wei, Ke; Wang, Jianming; Woods, Chris E.; Purcell, Nicole H.; Catalucci, Daniele; Akasaka, Takeshi; Bueno, Orlando F.; Vlasuk, George P.; Kaliman, Perla; Bodmer, Rolf; Smith, Layton H.; Ashley, Euan; Mercola, Mark; Brown, Joan Heller; Ruiz-Lozano, Pilar
Source
Subject
*CARDIAC hypertrophy
*HEART failure
*APELIN
*ATRIAL natriuretic peptides
*G protein coupled receptors
*MICE
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Language
ISSN
0028-0836
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 G?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 ?-arrestins or by pharmacological doses of apelin acting through G?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. [ABSTRACT FROM AUTHOR]