〔Abstract〕 Objective To investigate the role of G protein signal regulator 2(RGS2) in regulating the formation of angiotensin Ⅱ(AngⅡ)-induced aortic dissection. Methods C57BL/6 mice were divided into 3 groups: control group(n=10),AngⅡ group(n=20),AngⅡ+sh-RGS2 group(n=20).The AngⅡ group and AngⅡ+sh-RGS2 group established an aortic dissection model.The incidence of aortic dissection was evaluatedin vivo,and the phenotypic transformation of VSMC was evaluatedin vitroandin vivo. Results Knockdown of RGS2 largely counteracted AngⅡ-induced inhibition of αSMA,ACTA2 and MYH11,and suppressed AngⅡ-induced SPP1 and Vimentin in VSMC.The incidence of aortic dissection in AngⅡ group and AngⅡ+sh-RGS2 group were 45%(9/20) and 10%(2/20),respectively.Fewer elastic lamina thickening, aortic rupture, and aortic wall collagen fiber content were observed in AngⅡ+sh-RGS2 group compared to AngⅡ group.In addition, compared with the AngⅡ group, the maximum diameter of the aorta in the AngⅡ+sh-RGS2 group was significantly reduced(P<0.05).In addition, the ACTA2 and MYH11 proteins in the aorta of the AngⅡ+sh-RGS2 group were significantly higher than those in the AngⅡ group(P<0.01),while the RGS2,SPP1,and Vimentin proteins significantly decreased(P<0.01). Conclusion Knockdown of RGS2 inhibits the transformation of AngⅡ-induced VSMC from a contractile phenotype to a synthetic phenotype, thereby reducing the incidence of aortic dissection formation.