The Effect Of PCBP2 On The Development Of Pressure Overload Cardiac Hypertrophy In Mice And The Underlying Mechanism

Objective: To explore the effect of PCBP2 on the development of pressure overload cardiac hypertrophy in mice and the underlying mechanism.Methods: The pressure overload cardiac hypertrophy was constructed by transaortic constriction(TAC)in mice.PCBP2 and cardiac hypertrophic marker(Nppa,β-MHC)was detected in mice with cardiac hypertrophy.We isolated neonatal rat cardiomyocytes(NRCMs)and treated the cells with angiotensin II(Ang II)to induce hypertrophy.The effect of knockdown or overexpress the PCBP2 on the cardiomyocyte hypertrophy was observed.Results: The m RNA or proteins of Nppa and β-MHC of TAC group were higher than those of Sham group(P<0.05),but the m RNA and protein of PCBP2 were significantly lower of TAC group than those of Sham group.PCBP2 knockdown promoted angiotensin II(Ang II)-induced hypertrophy of cardiomyocytes,while PCBP2 overexpression obtained oppose effects.Furthermore,PCBP2 was shown to inhibit GPR56 expression by promoting its m RNA degeneration in cardiomyocytes.PCBP2 inhibits Ang II-induced hypertrophy of cardiomyocytes though promoting GPR56 m RNA degeneration.Conclusion: PCBP2 is an anti-hypertrophic factor by inhibiting GPR56 m RNA stability.PCBP2 involves the pressure overload-induced myocardial hypertrophy through regulation of GPR56 protein.Part 1.The effect of PCBP2 on the development of pressure overload cardiac hypertrophy in miceObjective: The pressure overload cardiac hypertrophy was constructed by transaortic constriction(TAC)in mice.To explore the effect of PCPB2 on the development of pressure overload cardiac hypertrophy in mice.Methods: 20 male C57BL/6 mice(age 8-10 weeks,weight 23-28 kg)were used to construct the model.The mice were divided into 2 groups: TAC group(TAC surgery)and Sham group(Sham surgery).Cardiac function was evaluated by echocardiography at postoperative 4 weeks.Also,the degree of cardiac hypertrophy was assessed with the ratio of heart weight/body weight(HW/BW).Real-time PCR was used to detected the m RNA of PCBP2 and cardiac hypertrophic marker(Nppa,β-MHC).Western blot was used to examined the protein of PCBP2 and cardiac hypertrophic markers(Nppa,β-MHC).The differences between the two groups were analyzed.Results: Compared with Sham group,cardiac hypertrophy and HW/BW ratio were significantly higher in TAC group(TAC vs Sham=8.23±1.88 mg/g vs 4.89±0.68 mg/g),but cardiac function was lower in TAC group(LVEF: TAC vs Sham=59.24±5.23% vs 74.15±5.68%;LVFS: TAC vs Sham=33.61±0.92% vs 43.87±1.37%)(P<0.05).The m RNA or proteins of Nppa and β-MHC of TAC group were higher than those of Sham group(P<0.05).However,both the m RNA and protein of PCBP2 were significantly lower than those of Sham group(P<0.05).Conclusions: PCBP2 was a negative factor for the development of pressure overload cardiac hypertrophy in mice.Part 2.The mechanism of PCBP2 affect the development of pressure overload cardiac hypertrophyObjective: To explore the underlying mechanism of PCBP2 affect the development of pressure overload cardiac hypertrophy.Methods: Primary neonatal rat cardiomyocytes(NRCMs)were separated and cultured.angiotensin II(Ang II)was used to induce cardiomyocyte hypertrophy.The effect of knockdown or overexpress the PCBP2 on the cardiomyocyte hypertrophy was observed.Whether GPR56 contributes to PCBP2 function in cardiomyocyte during cardiac hypertrophy was studied.Results: PCBP2 knockdown promoted angiotensin II(Ang II)-induced hypertrophy of cardiomyocytes,while PCBP2 overexpression obtained oppose effects.Furthermore,PCBP2 was shown to inhibit GPR56 expression by promoting its m RNA degeneration in cardiomyocytes.Conclusion: PCBP2 inhibits Ang II-induced hypertrophy of cardiomyocytes though promoting GPR56 m RNA degeneration.