Overexpression Of ACE2Inhibits The Proliferation Of Vascular Smooth Muscle Cells Via Downregulating Angiotensin II Type1Receptor And The Phosphorylation Of ERK1/2Level

Abstract:Objective: To evaluate whether over-expression of angiotensin-convertingenzyme(ACE)2protein could inhibit the proliferation of vascular smooth musclecells(VSMCs) through hinhibiting AT1R-ERK1/2signal pathway in rats.Methods：The effect of ACE2protein overexpression were detected via immunoblotafter recombinant ACE2lentiviral vector(lentiviral-ACE2) transfecting in culturedvascular smooth muscle cells in rats firstly. Then, the cells proliferation of VSMCstransfected by lentiviral ACE2was investigated cell counting kit-8.Finaly,angiotensinII type1recetpor protein and the phosphorylation of ERK1/2were detected byimmunoblot in cultured vascular smooth muscle cells in rats.Results: It is found that ACE2protein was significantly enhanced in time-dependentmanner after lentiviral-ACE2of MOI10transfected into VSMCs compared to that inuntransfection(1.22±0.06vs0.53±0.03，p<0.05，n=4）. It is found that ACE2protein was reduced in dose-dependent and time-dependent manner by Ang II inVSMCs. Meanwhile, angiotensin II type1receptor proten expression was enhancedin time-dependent manner.The phosphorylation of ERK1/2level was enhanced indose-dependent and time-dependent manner. The over-expression of ACE2proteincould inhibit proliferation of VSMCs obviously either in the absence or in thepresence of angiotensin II.Furthermore, the over-expression of ACE2protein coulddecrease angiotensinII type1receptor expression(0.72±0.08vs0.34±0.07，p<0.05，n=4) and the phosphorylation of ERK1/2（0.71±0.08vs0.43±0.06，p<0.05，n=4）either in the absence or in the presence of Ang II.Conclusion: These results indicate that over-expression of ACE2could attenuate theproliferation of VSMCs through inhibiting the signal pathway of AT1R-ERK1/2.Therefore,over-expression of ACE2protein may provide a new therapeutic strategy...