The Mechanism Of MiR-29b Mediated Endothelial-to-mesenchymal Transition To Improve Rats Models Of Pulmonary Arterial Hypertension Induced By Monocrotaline

Objective: To investigate the mechanism of microRNA-29 b through endothelial-to-mesenchymal transition on rats models of pulmonary arterial hypertension induced by monocrotaline.Methods: In our previous work,we found that miR-29 b expression was dramatically decreased during the process of pulmonary arterial hypertension by microRNA array analysis,indicating that miR-29 b may play an important regulatory role in the pathological process of pulmonary arterial hypertension.SD rats were randomly divided into four groups.Three groups were treated with a single intraperitoneal injection of MCT at a dose of 60 mg/kg to be modeled,the other received a single intraperitoneal injection of normal saline.Six rats of the MCT group were sacrificed at 2 weeks.The other rats were injected with miR-29 b mimics or negative control by tracheal spray,and sacrificed at 4 weeks.We measured the right ventricular systolic pressure(RVSP).The right ventricle(RV)and left ventricle plus septum(LV+S)were weighed respectively,and the weight ratio of(RV/(LV+S))was calculated as an index of RV hypertrophy.Hematoxylin-Eosin staining were examined to observe changes in pulmonary vascular endothelial cells.The expression of E-cadherin and α-SMA of each group were measured by immunohistochemical staining.Results: 1.MiR-29 b expression was decreased in rats models of pulmonary arterial hypertension induced by monocrotaline.2.Compared with the control group,RVSP and RV/(LV+S)was increased in the MCT group at 2 weeks and 4 weeks.MCT 4 weeks group shows significant damage of pulmonary vascular endothelial cells,hyperplasia and hypertrophy of vascular smooth muscles cells,and stenosis and occlusion of vascular.E-cadherin expression was decreased,while α-SMA expression were increased in pulmonary vascular endothelial cells of MCT 4 weeks group.3.After the injection with miR-29 b mimics,to compared with the MCT 4 weeks,RVSP and RV/(LV+S)was decreased in the MCT plus miR-29 b mimics group,and E-cadherin expression was increased,while α-SMA expression were decreased in pulmonary vascular endothelial cells.Conclusions: 1.Endothelial-to-mesenchymal transition of pulmonary artery endothelial cells were generated on rats models of pulmonary arterial hypertension induced by monocrotaline.2.MiR-29 b could prevent pulmonary artery remodeling and improve right ventricular hypertrophy on rats models.