Atractylenolide I restores HO-1 expression and inhibits Ox-LDL-induced VSMCs proliferation, migration and inflammatory responses in vitro.

Abstract

Pathogenesis of atherosclerosis is characterized by the proliferation and migration of vascular smooth muscle cells (VSMCs) and inflammatory lesions. The aim of this study is to elucidate the effect of atractylenolide I (AO-I) on smooth muscle cell inflammation, proliferation and migration induced by oxidized modified low density lipoprotein (Ox-LDL). Here, We found that atractylenolide I inhibited Ox-LDL-induced VSMCs proliferation and migration in a dose-dependent manner, and decreased the production of inflammatory cytokines and the expression of monocyte chemoattractant protein-1 (MCP-1) in VSMCs. The study also identified that AO-I prominently inhibited p38-MAPK and NF-κB activation. More importantly, the specific heme oxygenase-1 (HO-1) inhibitor zinc protoporphyrin (ZnPP) IX partially abolished the beneficial effects of atractylenolide I on Ox-LDL-induced VSMCs. Furthermore, atractylenolide I blocked the foam cell formation in macrophages induced by Ox-LDL. In summary, inhibitory roles of AO-I in VSMCs proliferation and migration, lipid peroxidation and subsequent inflammatory responses might contribute to the anti-atherosclerotic property of AO-I.

• Authors: Weifeng Li, Wenbing Zhi, Fang Liu, Zehong He, Xiuei Wang, Xiaofeng Niu
• Journal: Experimental cell research (Exp Cell Res) Vol. 353 Issue 1 Pg. 26-34 (04 01 2017) ISSN: 1090-2422 [Electronic] United States
• PMID: 28274716 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Lactones
• Lipoproteins, LDL
• Sesquiterpenes
• atractylenolide I
• oxidized low density lipoprotein
• HMOX1 protein, human
• Heme Oxygenase-1

Topics

• Animals
• Atherosclerosis (drug therapy, immunology, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Drug Evaluation, Preclinical
• Female
• Foam Cells (drug effects, physiology)
• Heme Oxygenase-1 (genetics, metabolism)
• Lactones (pharmacology)
• Lipoproteins, LDL (physiology)
• Male
• Mice
• Muscle, Smooth, Vascular (cytology)
• Myocytes, Smooth Muscle (drug effects, physiology)
• Rats, Sprague-Dawley
• Sesquiterpenes (pharmacology)