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Abstract Title:

Paeoniflorin Ameliorates Chronic Hypoxia/SU5416-Induced Pulmonary Arterial Hypertension by Inhibiting Endothelial-to-Mesenchymal Transition.

Abstract Source:

Drug Des Devel Ther. 2020 ;14:1191-1202. Epub 2020 Mar 19. PMID: 32256050

Abstract Author(s):

Min Yu, Liyao Peng, Ping Liu, Mingxia Yang, Hong Zhou, Yirui Ding, Jingjing Wang, Wen Huang, Qi Tan, Yanli Wang, Weiping Xie, Hui Kong, Hong Wang

Article Affiliation:

Min Yu

Abstract:

Background: Endothelial cells dysfunction is one of the hallmark pathogenic features of pulmonary arterial hypertension (PAH). Paeoniflorin (PF) is a monoterpene glycoside with endothelial protection, vasodilation, antifibrotic, anti-inflammatory and antioxidative properties. However, the effects of PF on PAH remain unknown.

Methods: Here, we investigated the efficacy of PF in the SU5416/hypoxia (SuHx) rat model of PAH. Human pulmonary arterial endothelial cells (HPAECs) were exposed to 1% Owith or without PF treatment.

Results: Hemodynamics analysis showed that prophylactic treatment with PF (300 mg/kg i.g. daily for 21 days) significantly inhibited chronic hypoxia/SU5416-induced elevations of right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index in rats. Meanwhile, PF significantly reduced pulmonary vascular remodeling, as well as alleviated collagen deposition in lungs and right ventricles in SuHx rats. Additionally, PF inhibited SuHx-induced down-regulation of endothelial marker (vascular endothelial cadherin) and up-regulation of mesenchymal markers (fibronectin and vimentin) in lung, suggesting that PF could inhibit SuHx-induced endothelial-to-mesenchymal transition (EndMT) in lung. Further in vitro studies confirmed that PF treatment suppressed hypoxia-induced EndMT in HPAECs, which was abolished by the knockdown of bone morphogenetic protein receptor type 2 (BMPR2) in HPAECs.

Conclusion: Taken together, our findings suggest that PF ameliorates BMPR2 down-regulation-mediated EndMT and thereafter alleviates SuHx-induced PAH in rats.

Study Type : Animal Study

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