Abstract:
:Pulmonary hypertension (PH) is a disease with a developmental origin characterized by obstructive vascular remodelling that is partially due to excessive pulmonary arterial smooth muscle cells (PASMCs) proliferation. Paeonol has important effects on vascular cell proliferation, migration, and inflammation, but researchers have not determined whether paeonol participates in the development and progression of pulmonary vascular remodelling. We explored the remarkable anti-proliferative effects of paeonol on hypoxic PASMCs, which are postulated to be mediated by the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signalling pathway. In this study, hypoxic rodent PH models, Western blotting, flow cytometry, immunochemistry, and morphometric analyses of the lung vasculature and right ventricle (RV) vessels were performed. Paeonol reversed hypoxia-induced increases in right ventricular function, right ventricular systolic pressure and thickening of medial walls. Meanwhile, paeonol ameliorated the hypoxia-induced PASMCs proliferation. Furthermore, paeonol modulated cell proliferation and cell cycle transitions from G0/G1 phase to S phase and G2/M phase in an ERK1/2-dependent manner. Our findings emphasize the central function of paeonol in regulating PASMCs proliferation in subjects with PH. Therefore, paeonol represents a potential novel therapeutic approach for the treatment of PH.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Zhang L,Ma C,Gu R,Zhang M,Wang X,Yang L,Liu Y,Zhou Y,He S,Zhu Ddoi
10.1016/j.ejphar.2018.07.017subject
Has Abstractpub_date
2018-09-05 00:00:00pages
257-265eissn
0014-2999issn
1879-0712pii
S0014-2999(18)30384-4journal_volume
834pub_type
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