Expression Of Sox17 In Rats With Pulmonary Hypertension And Its Effect On Pathological Process

Pulmonary hypertension(PH)is a serious pulmonary vascular disease characterized by pulmonary vascular remodeling and increased pulmonary vascular resistance.Its pathogenesis has not yet been fully elucidated.Sox17,as a transcription factor,plays important roles in cell fate determination and vascular development,and is considered a new risk factor for pulmonary arterial hypertension.This study aims to investigate the expression of Sox17 in the pathological process of pulmonary arterial hypertension and its influence on the pathological process.By establishing a rat model of pulmonary hypertension,this study used real-time quantitative fluorescent PCR,western blotting,and immunohistochemistry to analyze the expression of Sox17 in lung tissue.The results showed that the protein expression of Sox17 was significantly decreased in the rat PH model induced by hypoxia or monocrotaline.In order to further explore the role of Sox17 in PH,this study constructed rats with endothelial cell-specific Sox17-knockout rats,and then treated the rats with hypoxia or monocrotaline for modeling.The results showed that compared with control genotype rats,rats with endothelial cell-specific knockout of Sox17 showed elevated hemodynamic parameters,increased right heart hypertrophy index,and pulmonary vascular remodeling after hypoxia or monocrotaline treatment.In addition,this study also found a tendency for spontaneous PH in rats with endothelial cell-specific knockout of Sox17,suggesting that loss of Sox17 may be sufficient to initiate the disease process.In order to explore the molecular mechanism of Sox17 affecting the occurrence and development of pulmonary hypertension,we performed mass spectrometry analysis on the lung tissue of endothelial cell-specific Sox17 knockout monocrotaline model rats.The m RNA and protein levels of Cadm1 decreased continuously in the PBS control group,monocrotaline modeling group,and monocrotaline combined with endothelial cell-specific knockout of Sox17 modeling group,suggesting that Cadm1 may be one of the downstream effector molecules of Sox17 in the development of PH.In summary,this study preliminarily proves that the low expression of Sox17 in endothelial cells is one of the promoting factors for the development of PH,and the loss of Sox17 expression can induce spontaneous PH.These results provide new clues for further exploring the pathogenesis of pulmonary hypertension.