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

Biochem Biophys Res Commun. 2020 Nov 12;532(3):466-474. doi: 10.1016/j.bbrc.2020.08.076. Epub 2020 Sep 4.

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.

Keywords: Atherosclerosis; Autophagy; Celastrol; LXRα/ABCA1 signaling pathway; Lipid accumulation; Vascular smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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