Catalase Nanomaterials Regulate Ang II-induced RVSMCs Proliferation And Migration Via ROS/PTEN/NLRP3 Pathwa

Objective: To investigate the effect of Noncovalent interaction catalase(n(CAT))on Angiotensin Ⅱ(Angiotensin Ⅱ,n(CAT)).Ang Ⅱ)-induced proliferation and mi gration of Rat vascular smooth muscle cells(RVSMCs).Methods:Ang Ⅱ-induced RVSMCs proliferation model was established and treated with a certain concentration of n(CAT).Reactive oxygen species(ROS)scavenger NAC and PTEN inhibitor VO-Ohpic were used to investigate whether ROS/PTEN/NLRP3 signaling pathway mediates RVSMCs proliferation and migration.The activity of RVSMCs was detected by CCK-8,ROS level was detected by DCFHDA,cell migration was detected by scratch test,cell cycle distribution was detected by flow cytometry,and the expressions of synthetic proteins OPN,contractile proteins α-SMA and SM22α were detected by Western blot.And the expression levels of PTEN and NLRP3.Results: The effects of n(CAT)at three different concentrations(0.3,1,3 μg/ml)and three different time periods(24,48,72h)on the proliferation and migration of RVSMCs induced by 1 μM Ang Ⅱ were detected.The results showed that after tr eated with 0.3 μg/ml n(CAT)for 24 h,compared with the model group,the cell vi ability and ROS production were significantly decreased,the expression of α-SMA and SM22α,which reflected the contractile phenotype of RVSMCs,was increased,and the synthetic protein OPN was decreased(P<0.05).After 24 h treatment with0.3 μg/ml n(CAT),compared with the model group,the activity of RVSMCs and t he expression of ROS were significantly decreased(P<0.05).The distribution of S phase cells was significantly decreased(P<0.05).Cell migration was significantly inhibited(P<0.05).At the same time,the expressions of OPN and NLRP3 were si gnificantly decreased,while the expressions of α-SMA,SM22α and PTEN were sig nificantly increased(P<0.05).The addition of 1 m M ROS scavenger NAC to Ang Ⅱ and n(CAT)could reverse the effect of n(CAT): RVSMCs cell viability and R OS expression increased;The distribution of cells increased in S phase.The cell migration ability was enhanced.The expressions of OPN and NLRP3 increased wh ile those of α-SMA,SM22α and PTEN decreased(P<0.05).Similarly,the addition of 0.1 μM VO-Ohpic,a PTEN inhibitor,to Ang Ⅱ and n(CAT)resulted in the sa me effect as NAC in the previous part.Conclusions: n(CAT)can inhibit the proliferation and migration of RVSMCs,and its mechanism may be achieved by regulating ROS/PTEN/NLRP3 pathway.