1.Interventional effect of amniotic mesenchymal stem cells with high expression of angiotensin -converting enzyme 2 on pulmonary hypertension rats
Changfang Wu ; Hongzhe Zhang ; Jie Zha ; Zhen Gao
Acta Universitatis Medicinalis Anhui 2023;58(3):366-372
Objective:
To observe the interventional effects of human amniotic mesenchymal stem cells (hAMSCs) transfected with angiotensin converting enzyme 2 (ACE2) gene on monocrotaline-induced pulmonary arterial hypertension (PAH) in rats.
Methods :
① HAMSCs were transfected with lentivirus carrying ACE2 gene,and the expression of ACE2,insulin-like growth factor (IGF-1) ,granulocyte chemoattractant protein-2 ( GCP-2) gene,cell migration and tube formation ability was detected before and after transfection. ② Male,healthy,6-week-old SD rats were randomly divided into normal Control group ( Control group ) ,pulmonary hypertension group ( PAH group) ,human amniotic mesenchymal stem cell treatment group ( hAMSCs group) and ACE2-transfected human amniotic mesenchymal stem cell treatment group ( ACE2-hAMSCs group) .The mean pulmonary arterial pressure ( mPAP) and right ventricular hypertrophy index (RVHI) were measured 2 weeks after the model was established. The lumen size of pulmonary arterioles and the thickness of vessel wall were observed by HE staining.The mRNA expression levels of GCP-2 ,ACE2 ,α-actin and angiotensin Ⅱ ( Ang Ⅱ ) in lung tissue were determined by QPCR .
Results :
In vitro cell experiments showed that the cell migration ability and tube formation ability of ACE2- hamscs were higher than those of pure hAMSCs (P<0. 05) .Ace2-hamscs up-regulated the mRNA expressions of ACE2 and pro-angiogenic factors IGF-1 and GCP-2 (P< 0. 01) .After 2 weeks of intervention,the mPAP and cardiac RV/ LV + S of the PAH group significantly increased compared with the normal control group (P<0. 01) ,and the mPAP and cardiac RV/ LV + S of the ACE2-hAMSCs group significantly decreased compared with the PAH and hAMSCs groups (P <0. 01 ) . Compared with PAH group,the mRNA expression level of ACE2 significantly increased in the lung tissue of ACE2-hamscs group.
Conclusion
ACE2-hAMSCs can significantly reduce the mean pulmonary arterial pressure of monocrotaline (MCT) -induced PAH rat model,and significantly improve pulmonary vascular and right ventricular remodeling.The therapeutic effect of ACE2-hamscs is significant in hAMSCs group. It is considered that ACE2-hAMSCs may not only promote the paracrine effect of hAMSCs,The expression of provascular growth factors GCP2 and IGF-1 can repair the injured pulmonary vascular endothelial cells and reduce the high pressure of pulmonary artery.Moreover,the high expression of ACE2 in hAMSCsis related to the regulation of RAS.