Regulator of G Protein Signaling 6 Facilities Cardiac Hypertrophy by Activating Apoptosis Signal–Regulating Kinase 1–P38/c‐JUN N‐Terminal Kinase 1/2 Signaling
التفاصيل البيبلوغرافية
العنوان:
Regulator of G Protein Signaling 6 Facilities Cardiac Hypertrophy by Activating Apoptosis Signal–Regulating Kinase 1–P38/c‐JUN N‐Terminal Kinase 1/2 Signaling
Background Regulator of G protein signaling 6 ( RGS 6) is an important member of the RGS family and produces pleiotropic regulatory effects on cardiac pathophysiology. However, the role of RGS 6 protein in cardiomyocytes during angiotensin II – and pressure overload–induced cardiac hypertrophy remain unknown. Methods and Results Here, we used a genetic approach to study the regulatory role of RGS 6 in cardiomyocytes during pathological cardiac hypertrophy. RGS 6 expression was significantly increased in failing human hearts and in hypertrophic murine hearts. The extent of aortic banding–induced cardiac hypertrophy, dysfunction, and fibrosis in cardiac‐specific RGS 6 knockout mice was alleviated, whereas the hearts of transgenic mice with cardiac‐specific RGS 6 overexpression exhibited exacerbated responses to pressure overload. Consistent with these findings, RGS 6 also facilitated an angiotensin II –induced hypertrophic response in isolated cardiomyocytes. According to the mechanistic studies, RGS 6 mediated cardiac hypertrophy by directly interacting with apoptosis signal–regulating kinase 1, which further activates the P38‐c‐ JUN N‐terminal kinase 1/2 signaling pathway. Conclusions Based on our findings, RGS 6 aggravates cardiac hypertrophy, and the RGS 6‐apoptosis signal–regulating kinase 1 pathway represents a potential therapeutic target to attenuate pressure overload–driven cardiac remodeling.
