Celastrol suppresses lipid accumulation through LXRα/ABCA1 signaling pathway and autophagy in vascular smooth muscle cells.

Abstract

The uptake of modified low-density lipoprotein (LDL) and the accumulation of lipid droplets induce the formation of vascular smooth muscle cells (VSMCs)-derived foam cells, thereby promoting the development and maturation of plaques and accelerating the progression of atherosclerosis. Celastrol is a quinine methide triterpenoid isolated from the root bark of traditional Chinese herb Tripterygium wilfordii. It possesses various biological properties, including anti-obesity, cardiovascular protection, anti-inflammation, etc. In the present study, we found that celastrol significantly reduced lipid accumulation induced by oxidized LDL (ox-LDL) in VSMCs. Mechanistically, celastrol up-regulated adenosine triphosphate-binding cassette transporter A1 (ABCA1) expression through activating liver X receptor α (LXRα) expression, which contributed to inhibit lipid accumulation in VSMCs. Meanwhile, celastrol decreased lipid accumulation by triggering autophagy in VSMCs. Therefore, these findings supported celastrol as a potentially effective agent for the prevention and therapy of atherosclerosis.

• Authors: Yaning Shi, Shuang Jiang, Tanjun Zhao, Yongzhen Gong, Duanfang Liao, Li Qin
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 532 Issue 3 Pg. 466-474 (11 12 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 32892949 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• ABCA1 protein, human
• ATP Binding Cassette Transporter 1
• Lipoproteins, LDL
• Liver X Receptors
• NR1H3 protein, human
• Pentacyclic Triterpenes
• Triterpenes
• oxidized low density lipoprotein
• celastrol

Topics

• ATP Binding Cassette Transporter 1 (metabolism)
• Atherosclerosis (drug therapy, metabolism, prevention & control)
• Autophagy (drug effects)
• Cells, Cultured
• Foam Cells (drug effects, metabolism, pathology)
• Humans
• Lipid Metabolism (drug effects)
• Lipoproteins, LDL (metabolism, pharmacology)
• Liver X Receptors (metabolism)
• Muscle, Smooth, Vascular (cytology, drug effects, metabolism)
• Myocytes, Smooth Muscle (cytology, drug effects, metabolism)
• Pentacyclic Triterpenes
• Signal Transduction (drug effects)
• Triterpenes (pharmacology)