The Influence of Bosentan on MicroRNA-27a/PPAR[gamma]/ET-1 Signaling Pathway in Pulmonary Artery Hypertension

Pulmonary artery hypertension (PAH) is a common and serious disease which is characterized by pulmonary vascular remodeling. Bosentan (BST) is the first approved oral targeted drug of endothelin-1 (ET-1) receptor antagonists for the treatment of PAH. MicroRNA-27a (miR-27a) and peroxisome proliferato...

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Bibliographic Details
Published in:Pediatric cardiology 2021-06, Vol.42 (5), p.1141
Main Authors: Zhao, Haizhao, Guo, Aili, Wang, Minmin, Cai, Zhifeng, Liu, Xiaoyue, Kong, Qingyu, Zhao, Cuifen
Format: Article
Language:English
Subjects:
Bosentan
Cellular signal transduction
Drug approval
Endothelin
Hypertension
MicroRNA
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Summary:Pulmonary artery hypertension (PAH) is a common and serious disease which is characterized by pulmonary vascular remodeling. Bosentan (BST) is the first approved oral targeted drug of endothelin-1 (ET-1) receptor antagonists for the treatment of PAH. MicroRNA-27a (miR-27a) and peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]) were found to be related to the pathogenesis of PAH. To further explore the signal transduction mechanism of BST in the treatment of PAH, we examined the effects of BST on endothelin receptors, miR-27a, and PPAR[gamma]. Meanwhile, the influence of miR-27a in the formation and development of PAH was discussed. Our results demonstrated that during the pathophysiology of PAH, miR-27a, PPAR[gamma], and ET-1 were cross-inhibited, which indicated that the miR-27a/PPAR[gamma]/ET-1 signaling pathway was dysregulated; in addition, BST could competitively bind to ET-1 receptors and inhibit the miR-27a/PPAR[gamma]/ET-1 signaling pathway, thereby delaying the proliferation of PASMCs and affecting the development of PAH. Our results give a new understanding of the pathogenesis and treatment of PAH and provide more reliable evidence for the application of BST in the treatment of PAH in the clinic.
ISSN:0172-0643
DOI:10.1007/s00246-021-02592-3