Experimental Study on the Effect and Mechanism of TWIST1 Promoting Pulmonary Vascular Remodeling in a Rat Model of Pulmonary Arterial Hypertension by Activation of Autophagy
Experimental Study on the Effect and Mechanism of TWIST1 Promoting Pulmonary Vascular Remodeling in a Rat Model of Pulmonary Arterial Hypertension by Activation of Autophagy
Objective To investigate the effect and mechanism of Twist-related protein 1(TWIST1)on pulmonary vascular remodeling induced by monocrotaline(MCT)in pulmonary arterial hypertension(PAH)rats.Methods A total of 50 healthy male Sprague Dawley(SD)rats were randomly divided into five groups including control group,MCT-treated group,MCT and dimethyl sulfoxide(DMSO)-treated group,MCT and harmine-treated group MCT and hydroxychloroquine(HCQ)-treated group.The right ventricle systolic pressure(RVSP)was measured,right ventricular hypertrophy index(RVHI)and percentage of medial wall thickness(MT％)to assess the development of PAH.The protein levels of TW1ST1,autophagy markers LC3B and RND3 were determined using western blot.Results Compared with control group,expressions of TWIST1 and LC3B were increased by 2.32±0.22 folds and 0.87±0.19 folds in MCT-induced PAH group,with significant differences(t=15.812,11.227,all P＜0.00 1),while the protein level of RND3 in MCT-induced PAH rats was decreased by 0.32±0.07 folds compared with control group,with significant difference(t=-13.003,P＜0.001).Administration of TWIST1 inhibitor Harmine or autophagy inhibitor hydroxychloroquine significantly suppressed MCT-induced increase in LC3B and down-regulation of RND3 expression,and reduced RVSP,RVHI and MT％expressions in MCT-induced PAH rats,with significant differences(t=-24.277～16.636,all P＜0.001).Conclusion TWIST1 promotes pulmonary vascular remodeling by inducing autophagy activation,thus promoting the occurrence and development of PAH.
关键词
肺动脉高压/血管重塑/Twist相关蛋白1
Key words
pulmonary arterial hypertension/vascular remodeling/Twist-related protein 1
维普
万方数据