1. Mesenchymal stromal cell-derived exosomes improve pulmonary hypertension through inhibition of pulmonary vascular remodeling.
- Author
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Zhang S, Liu X, Ge LL, Li K, Sun Y, Wang F, Han Y, Sun C, Wang J, Jiang W, Xin Q, Xu C, Chen Y, Chen O, Zhang Z, and Luan Y
- Subjects
- Animals, Cells, Cultured, Disease Models, Animal, Exosomes metabolism, Hypertension, Pulmonary chemically induced, Hypertension, Pulmonary pathology, Hypertrophy, Right Ventricular pathology, Hypertrophy, Right Ventricular therapy, Mesenchymal Stem Cells metabolism, Rats, Exosomes physiology, Hypertension, Pulmonary therapy, Mesenchymal Stem Cells cytology, Vascular Remodeling
- Abstract
Background: Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, right ventricular hypertrophy and failure. So far no effective treatment exists for this disease; hence, novel approaches are urgently needed. The aim of the present research was to observe the treatment effect of mesenchymal stromal cell derived exosomes and reveal the mechanism., Methods: Monocrotaline (MCT)-induced PH in rats and hypoxia-induced cell damage model were established, respectively. Exosomes derived from the supernatant of human umbilical cord mesenchymal stem cells (MSC-exo) were injected into MCT-PH model rat or added into the cells cultured medium. Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods were used in vivo and vitro., Results: The results showed that MSC-exo could significantly attenuate right ventricular (RV) hypertrophy and pulmonary vascular remodelling in MCT-PH rats. In the cell culture experiments, we found that MSC-exo could significantly inhibit hypoxia-induced pulmonary arterial endothelial cell (PAEC) apoptosis and pulmonary arterial smooth muscle cells (PASMC) proliferation. Furthermore, the pulmonary arterioles endothelial-to-mesenchymal transition (EndMT) was obviously suppressed. Moreover, the present study suggest that MSC-exo can significantly upregulate the expression of Wnt5a in MCT-PH rats and hypoxic pulmonary vascular cells. Furthermore, with Wnt5a gene silencing, the therapeutic effect of MSC-exo against hypoxia injury was restrained., Conclusions: Synthetically, our data provide a strong evidence for the therapeutic of MSC-exo on PH, more importantly, we confirmed that the mechanism was associated with up-regulation of the expression of Wnt5a. These results offer a theoretical basis for clinical prevention and treatment of PH.
- Published
- 2020
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