Expression of Gsα in mice with cardiac hypertrophy and effects of cardiac-specific Gsα deletion on heart development in young mice

Di-san junyi daxue xuebao

YIN Ping¹  SU Li¹  ZHAO Qi¹  SHI Yujun² 

[1] Department of Cardiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400014;Department of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, China ;

关键词: transverse aortic constriction;    cardiac hypertrophy;    heart development;    gsα;    tamoxifen;    gene deletion;   

DOI  :  10.16016/j.1000-5404.202101167

来源: DOAJ

【 摘 要 】

Objective To detect the expression profile of alpha-subunit of the stimulatory G protein (Gsα) in a mouse model of pressure overload-induced cardiac hypertrophy by transverse aortic constriction (TAC), and investigate the effects of cardiac-specific Gsα deletion on the cardiac development in young mice. Methods Ten healthy adult male C57BL/6 mice were randomized equally into model group (TAC) and sham operation (Sham) group. The mice of the TAC group were inflicted with TAC to construct a mouse model of pressure overload induced myocardial hypertrophy. Four weeks after surgery, echocardiography was employed to assess the left cardiac function, histopathological staining was used to observe the myocardial structure, and RT-qPCR as well as Western blotting were performed to detect the expression of Gsα in the myocardial tissues of the mice. In addition, a Myh6-MerCreMer+/-/Gsαfl/fl (MCM/ Gsαfl/fl) mouse model was established by hybridization of Gsαfl/fl mice and Myh6-MerCreMer mice using Cre/Loxp system. Then lactating female MCM/Gsαfl/fl mice were intraperitoneally injected with tamoxifen (TMX, 20 mg/mL) for 10 consecutive days from the delivery day, transferring TMX to the young mice through lactation to construct inductive cardiac-specific Gsα-deficient pups. The body weight and survival rate of the pups were subsequently recorded, and the myocardial structural changes were detected using histological staining. Results As compared with the Sham group, the mice in the TAC group showed significantly increased thickness of end-diastolic left ventricular posterior wall (LVPWd) (P < 0.01) and end-diastolic interventricular septum (IVSd) (P < 0.05), while decreased end-diastolic left ventricular internal diameter (LVIDd) (P < 0.05), suggesting the onset of compensatory cardiac hypertrophy. Histopathological analysis indicated greater cross-sectional area of myocardium and higher perivascular fibrosis progression rate (P < 0.01), and the mRNA and protein levels of Gsα were significantly increased in the TAC group (P < 0.05). Compared to the control group, the TMX-induced Gsα-deficient pups showed significant growth retardation and reduction of body weight (P < 0.05), as well as reduced overall heart size. Conclusion The expression of Gsα is up-regulated in cardiac hypertrophy induced by pressure overload. Postnatal cardiac Gsα deletion retards the growth of young mice and inhibits their heart development, indicating that Gsα may be involved in heart physiological development and process of compensatory cardiac hypertrophy.

【 授权许可】

Unknown