Carboxyl Terminal Modulator Protein Alleviates Pressure Overload Induced Cardiac Hypertrophy

Objective: we will explore the influence and underlying molecular mechanism of CTMP on pressure overload induced cardiac hypertrophy mice.Methods: The research selected the male C57BL/6 mice,weight from 23.50-27.5g,whose age is 8-10 weeks.Different types of mice of ?-MHC-MCM?CTMP-Flox?CTMPCKO?CTMP-TG were divided into two groups,including the AB group performed an operation of aortic biding and Sham group.After 4 weeks,cardiac function was measured by echocardiography and hemodynamic.Mice were autopsy carefully to measure successively the Heart Weight(HL)?Lung Weight(LW)and Tiba Length(TL).Then,the ratio of HW/BW,HW/TL and LW/BW was calculated.When heart sections were stained with hematoxylin and eosin(H&E)and picrosirius red(PSR),cardiomyocyte myocyte cross-sectional area and cardiac fibrosis was observed and measured.The technology of Quantitative real-time PCR was used to detect the markers which represent cardiac hypertrophy and myocardial fibrosis(ANP?BNP??-MHC;Collagen I??Collagen??CTGF).The protein levels of CTMP in MAPK and Akt pathways was detected by western blotting technology,to explore the mechanism that CTMP inhibit of myocardial hypertrophy.Results: 1?In the AB group,comparing the control group(?-MHC-MCM mice?CTMPFlox mice),the CTMP-CKO significantly increased the degree of myocardial hypertrophy,myocardial cell cross-sectional area and myocardial collagen content,significantly worse cardiac function,as well as markers of myocardial hypertrophy and fibrosis markers increased significantly.2?In the AB group,comparing the CTMP-NTG group(?-MHC-MCM mice),the CTMP-CKO significantly reduceded the degree of myocardial hypertrophy,myocardial cell cross-sectional area and myocardial collagen content,significantly better cardiac function,as well as markers of myocardial hypertrophy and fibrosis markers declined significantly.3?In the study of signaling pathways,CTMP affected the Phosphorylation level of Akt and downstream effector of Akt,indicating CTMP interacted with Akt signaling pathway.Conclusions: CTMP interacted with Akt to effect the AKT-GSK3? signaling pathway,the degree of myocardial hypertrophy,myocardial cell cross-sectional area,myocardial collagen content and significantly cardiac function.