the sanford - burnham medical research institute s animal care & use program is accredited by aaalac international and a multiple project assurance a3053 - 1 is on file in the olaw , dhhs . both apj and apelin lines ( male and female ) were in c57bl/6 genetic background in a 99%100% purity , as demonstrated by microsatelite analysis ( radil ) . for detailed methods , both apj and apelin lines ( male and female ) were in c57bl/6 genetic background in a 99%100% purity , as demonstrated by microsatelite analysis ( radil ) . for detailed methods ,
cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues1 . here 
 we report that genetic loss of apj confers resistance to chronic pressure overload by dramatically 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 mechano - sensor . 
 activation of apj by stretch increases cardiomyocyte cell size and induces molecular markers of hypertrophy . whereas apelin stimulates apj to activate gi 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 gi . 
 taken together , our data indicate that apj is a bifunctional receptor for both mechanical stretch and for the endogenous peptide apelin . by sensing the balance between these stimuli , apj occupies a pivotal point linking sustained overload to cardiomyocyte hypertrophy .