STIM1 silencing prevents pressure-overload induced cardiac hypertrophy in mice

Abstract

STromal Interaction Molecule 1 (STIM1), a membrane protein of the endoplasmic reticulum (ER), has recently been proposed as a positive regulator of cardiomyocyte growth by promoting calcium (Ca2+) entry through the plasma membrane and the activation of Ca2+-mediated signaling pathways (Circulation, 2011).

To further extend this observation, we studied the impact of STIM1 silencing in pressure-overload induced mouse model of cardiac hypertrophy using recombinant Associated Adenovirus 9 (AAV9)-mediated gene silencing. C57/Bl6 Mice were injected with saline (noAAV) or with rAAV9 expressing shRNA against STIM1 (shSTIM1) or a control shRNA (shScr) at 1E+11 viral genome by tail vein injection. Three weeks later, Transverse Aortic Constriction (TAC) surgery was performed (4 experimental groups: sham, TAC-noAAV, TAC-shScr and TAC-shSTIM1). In contrast to TAC-noAAV or TAC-shScr, the rAAV9-shSTIM1 treated animals developed significantly reduced cardiac hypertrophy developed as assessed by echocardiogtaphy and hemodynamics three weeks after surgery. TAC-ShSTIM1 however displayed left ventricular dilation and a non-significant trend for depressed systolic function.

These results indicate STIM1 as a key regulator of cardiac hypertrophy.