Protective effect of the RGS2‐eIF2Bε binding domain (RGS2eb) in cardiac hypertrophy

Abstract

Regulator of G protein signalling 2 (RGS2) is known to play a protective role in maladaptive cardiac hypertrophy and heart failure via its ability to inhibit Gq and Gs mediated GPCR signalling. Recently, we have demonstrated that RGS2 can also inhibit protein translation, which would be expected to attenuate cell growth. This novel, G protein‐independent inhibitory effect has been mapped to a 37 a.a. domain (RGS2eb) within RGS2 that binds to eukaryotic initiation factor 2B (eIF2B). When expressed on its own in neonatal rat cardiomyocytes, RGS2eb attenuates both protein synthesis and hypertrophy induced by Gq and Gs activating agents. The objective of this study is to further elucidate the cardioprotective role of RGS2eb by determining whether mice with targeted cardiac expression of RGS2eb show resistance to the development of hypertrophy in comparison to wild‐type (WT) controls. Cardiac hypertrophy was induced by one month of transverse aortic constriction (TAC). RGS2ebtransgenic mice were found to have a significantly lower left ventricle/body weight ratio compared to WT TAC mice. In addition, the expression of hypertrophy markers, such as alpha natriuretic peptide (ANP), was decreased in RGS2eb TAC mice compared to WT TAC animals. These results suggest that RGS2eb, via its inhibition of protein synthesis, may be decreasing the severity of cardiac hypertrophy and aiding in the maintenance of cardiac function.