Study On The Role And Mechanism Of Actin Nucleation Factor Arp2/3 Complex In Cardiomyocyte Hypertroph

Objective: Revealing the key role of the Arp2/3 complex(Actin-related protein-2/3 complex)in cardiomyocyte hypertrophy and exploring its functional mechanism.Methods: The mouse model of cardiac hypertrophy was constructed via using transverse aortic constriction(TAC).The gene expression level of the Arp2/3 complex was assayed by RT-q PCR in the cardiac hypertrophy.The gene expression level of Arp2/3 complex was assayed by RT-q PCR in angiotensin II(Ang II)induced cardiomyocyte hypertrophy.The normal formation of Arp2/3 complexes was disrupted via using si ARPC2.Subsequently,it is treated by PBS and Ang II,respectively.Expression levels of Nppa,Nppb and Myh7 were assayed by RT-q PCR and the cross-sectional area of cardiomyocytes was measured to study the role of Arp2/3 complex in Ang II-induced cardiomyocyte hypertrophy.Upstream activating proteins of Arp2/3 complexes were assayed by western blot.Cardiomyocytes were treated with CK666(an inhibitor of Arp2/3 complex)and CK689(inactive form of CK666),respectively.Subsequently,it is treated by PBS and Ang II,respectively.Expression levels of Nppa,Nppb and Myh7 were assayed by RT-q PCR and the cross-sectional area of cardiomyocytes was measured to study the correlation between inhibition of Arp2/3 complex and Ang II-induced cardiomyocyte hypertrophy.The phosphorylation level of ERK1/2 was assayed by western blot and the relationship between Arp2/3 complex and ERK1/2 signaling pathway was explored.Results: Compared with the sham group,Arp2/3 complex was upregulated in TAC-induced cardiac hypertrophy.Similarly,Arp2/3 complex was upregulated in the Ang II-induced cardiomyocyte hypertrophy compared with the control group.Compared with the si NC +Ang II group,the cross-sectional area of cardiomyocytes in the si ARPC2 + Ang II group was significantly reduced,and the expression levels of Nppa,Nppb and Myh7 were significantly decreased.Compared with the control group,upstream activating proteins including SPIN90,Rac1 and WAVE-2 of Arp2/3 complex were upregulated in the Ang II group.In addition,the cross-sectional area of cardiomyocytes in the CK666 + Ang II group was significantly reduced and expression levels of Nppa,Nppb and Myh7 were significantly deceased compared with the Ang II group.The cross-sectional area of cardiomyocytes and expression levels of Nppa,Nppb and Myh7 in the CK689 + Ang II group have no significant differences.Compared with the control group,the phosphorylation level of ERK1/2 in the Ang II group was increased.There was no significant difference in the phosphorylation level of ERK1/2in the CK666 group and the CK689 group.Compared with Ang II group,the phosphorylation level of ERK1/2 in CK666 + Ang II group was reduced while there was no difference in the phosphorylation level of ERK1/2 in CK689 + Ang II group.Conclusion: Arp2/3 complex is a key factor in the Ang II induced cardiomyocyte hypertrophy.It may play a critical role in cardiomyocyte hypertrophy through regulating the ERK1/2 signaling pathway.