[PPARγ signal transduction pathway in the foam cell formation induced by visfatin]

Sheng Li Xue Bao. 2010 Oct 25;62(5):427-32.
[Article in Chinese]

Abstract

The aim of the present study was to investigate the role of peroxisome proliferator-activated receptor γ (PPARγ) signal transduction pathway in the expression of ATP binding cassette transporter A1 (ABCA1) and acyl-CoA:cholesterol acyltransferase 1 (ACAT1) induced by visfatin and to discuss the mechanism of foam cell formation induced by visfatin. THP-1 monocytes were induced into macrophages by 160 nmol/L phorbol myristate acetate (PMA) for 48 h, and then the macrophages were exposed to visfatin and PPARγ activator rosiglitazone, respectively. The expressions of PPARγ, ABCA1 and ACAT1 mRNA and protein were determined by RT-PCR and Western blot respectively. The contents of total cholesterol (TC) and free cholesterol (FC) were detected by enzyme fluorescence analysis. The content of cholesterol ester (CE) was calculated by the difference between TC and FC. The results showed that visfatin decreased the mRNA and protein expressions of PPARγ and ABCA1, increased the mRNA and protein expressions of ACAT1, and increased the contents of FC and CE in a concentration-dependent manner. These above effects of visfatin were inhibited by rosiglitazone in a concentration-dependent manner. These results suggest that visfatin may down-regulate the ABCA1 expression and up-regulate the ACAT1 expression via PPARγ signal transduction pathway, which decreases the outflow of FC, increases the content of CE, and then induces foam cell formation.

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Acetyl-CoA C-Acetyltransferase / genetics
  • Acetyl-CoA C-Acetyltransferase / metabolism*
  • Cell Differentiation
  • Cell Line
  • Cholesterol Esters / metabolism
  • Foam Cells / cytology*
  • Humans
  • Macrophages / cytology
  • Monocytes / cytology
  • Nicotinamide Phosphoribosyltransferase / pharmacology*
  • PPAR gamma / agonists
  • PPAR gamma / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rosiglitazone
  • Signal Transduction
  • Thiazolidinediones / pharmacology

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Cholesterol Esters
  • PPAR gamma
  • RNA, Messenger
  • Thiazolidinediones
  • Rosiglitazone
  • ACAT1 protein, human
  • Acetyl-CoA C-Acetyltransferase
  • Nicotinamide Phosphoribosyltransferase