The Protective of hUC- MSCs Derived Exosomes on Pulmonary Vascular Remodeling in Experimental Pulmonary Hypertension

Abstract Pulmonary hypertension (PH) is a life-threatening disease, so far no effective method for it. Therefore, the main aim of the present study was to investigate the protective effect of exosomes derived from human umbilical cord msenchymal stem cells (hUC-MSCs) on PH vascular remodeling and reveal the underlying mechanism. We established monocrotaline-induced PH (MCT-PH) rats and hypoxia induced pulmonary artery smooth muscle cells (H-PASMC) model in vivo and vitro . Exosomes derived from hUC-MSCs (hUC-MSC-EXO) were administration, respectively. Post-operation, our results showed that hUC-MSC-EXO significantly reduced the right ventricular systolic pressure (RVSP) and the right ventricular hypertrophy index (RVHI), inhibited pulmonary vascular remodeling. Furthermore, the hypoxia-induced PASMC proliferation was obviously inhibited in vitro . More-importantly, the results showed that the protein expression levels of BMPR2, BMP-4 and BMP-9 were significantly increased, but the levels of nuclear factor-κB (NF-κB) p65 and bone morphogenetic protein (BMP) antagonists Gremlin-1 were significantly decreased in hUC-MSC-EXO than that in MCT-PH and hypoxia-induced PASMC groups in vivo and vitro , respectively. Taken together, this present study provided the firm information for the use of this new method in treatment of PH, and the mechanism was associated with regulation of BMP signaling pathway.