Magnesium lithospermate B prevents phenotypic transformation of pulmonary arteries in rats with hypoxic pulmonary hypertension through suppression of NADPH oxidase.

Abstract

Magnesium lithospermate B (MLB) shows multiple biological activities including anti-oxidation and anti-proliferation in various diseases. However, the function of MLB in pulmonary arterial hypertension (PAH) is still unknown. This study aims to investigate the effect of MLB on hypoxia-induced phenotypic transformation of pulmonary arterial smooth muscle cells (PASMCs) and the underlying mechanisms. SD rats (or PASMCs) were exposed to 10% O2 for 3 weeks (or 3% O2 for 48 h) along with MLB or NADPH oxidase （NOX） inhibitor intervention. The effects of MLB on hemodynamics, pulmonary vascular remodeling and phenotypic transformation of PASMCs were observed first. Then, its effects on the protein levels of NOX (NOX2 and NOX4), ERK and p-ERK were examined. The results showed that MLB prevented the elevation in right ventricular systolic pressure and the increase in ratio of wall thickness to vessel external diameter of pulmonary arteries in PAH rats, and attenuated phenotypic transformation of PASMCs (decrease in α-smooth muscle actin while increase in osteopontin), accompanied by downregulation of NOX (NOX2 and NOX4) protein levels, decrease of ROS and H2O2 production, and suppression of the phosphorylation of ERK. NOX inhibitor (VAS2870) achieved similar results to that of MLB did in the hypoxia-treated PASMCs. Based on the observations, we conclude that MLB is able to prevent phenotypic transformation of pulmonary arteries in hypoxic PAH rats through suppression of NOX/ROS/ERK pathway, and MLB might have the potentials in PAH therapy.

• Authors: Tao Li, Xiu-Ju Luo, E-Li Wang, Nian-Sheng Li, Xiao-Jie Zhang, Feng-Lin Song, Jin-Fu Yang, Bin Liu, Jun Peng
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 847 Pg. 32-41 (Mar 15 2019) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 30659826 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• Reactive Oxygen Species
• lithospermate B
• Hydrogen Peroxide
• NADPH Oxidases
• Magnesium

Topics

• Animals
• Cell Line
• Drugs, Chinese Herbal (pharmacology)
• Hydrogen Peroxide (metabolism)
• Hypertension, Pulmonary (drug therapy, metabolism)
• Hypoxia (drug therapy, metabolism)
• Magnesium (pharmacology)
• Male
• Myocytes, Smooth Muscle (drug effects, metabolism)
• NADPH Oxidases (metabolism)
• Phosphorylation (drug effects)
• Pulmonary Artery (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Vascular Remodeling (drug effects)