Paeonol regulates hypoxia-induced proliferation of pulmonary artery smooth muscle cells via EKR 1/2 signalling.

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.

• Authors: Lixin Zhang, Cui Ma, Rui Gu, Min Zhang, Xiaoying Wang, Lin Yang, Ying Liu, Yutian Zhou, Siyu He, Daling Zhu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 834 Pg. 257-265 (Sep 05 2018) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 30053410 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Acetophenones
• paeonol
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Acetophenones (pharmacology, therapeutic use)
• Animals
• Cell Cycle (drug effects)
• Cell Hypoxia (drug effects)
• Cell Proliferation (drug effects)
• Heart Ventricles (drug effects, pathology)
• Hypertension, Pulmonary (drug therapy, pathology)
• Hypertrophy (drug therapy)
• Male
• Mice
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Myocytes, Smooth Muscle (cytology, drug effects, metabolism, pathology)
• Pulmonary Artery (cytology, pathology)
• Rats
• Signal Transduction (drug effects)
• Vascular Remodeling (drug effects)