Transfer of human hepatocyte growth factor reduces inflammation and prevents pulmonary arterial remodeling in monocrotaline-induced

摘要

Inflammation and endothelial dysfunction contribute to the pathogenesis and development of pulmonary arterial hypertension (PAH). This study was to investigate the therapeutic effect of human hepatocyte growth factor (HGF) gene transfer on monocrotaline (MCT) induced PAH rat models. PAH was induced by injecting MCT for 4 weeks. The rats were randomly assigned to phosphate buffered saline control group, MCT group, and HGF treatment group. After 2 weeks of induction, measures of mean pulmonary artery pressure (mPAP), weight ratio of the RV to the LV plus septum, percent wall thickness index (TI) and area index (AI) were significantly increased in MCT-group and HGF treatment-group compared with those in control group (P < 0.05). Those measurements in MCT-group were significantly higher than those in HGF treatment-group (P < 0.05). IL-6 significantly decreased in HGF treatment-group compared with MCT-group, but higher than that of control group (all P < 0.05). IL-10 in HGF treatment-group significantly increased compared with MCT-group, but lower than that of control group (all P < 0.05). Endothelial microparticles (EMP) started to decrease in the HGF treatment-group 3 days after treatment and was most significant after 1 and 2 weeks of treatment (all P < 0.05). Our results showed that transfer of human HGF may attenuate the inflammatory cell infiltrate, reduce the expression of inflammatory factors, and those effects are possibly due to the inhibition of EMP production which may decrease pulmonary vascular wall damage in PAH.