FGF21 protects against ox-LDL induced apoptosis through suppressing CHOP expression in THP1 macrophage derived foam cells

BMC Cardiovasc Disord. 2015 Jul 30:15:80. doi: 10.1186/s12872-015-0077-2.

Abstract

Background: FGF21,as a member of the fibroblast growth factor superfamily, is an important endogenous regulator to systemic glucose and lipid metabolism. Elevated serum FGF21 levels have been reported in subjects with coronary heart disease and carotid artery plaques. The formation and apoptosis of foam cell, induced by ox-LDL and oxysterols, are key steps in the development of atherosclerosis.

Methods: In this study, THP1 derived macrophages were induced into foam cells by ox-LDL or sterols. The formation and apoptosis of foam cells treated with or without FGF21 were analyzed.

Results: We demonstrated that the accumulation of cholesterol was decreased after FGF21 treatment in THP1 macrophage derived foam cells. Consistently, the apoptosis of macrophage was alleviated dramatically with FGF21 treatment. ERK1/2 knockdown didn't abrogate the effect of FGF21 on THP1 macrophage derived foam cells. However, FGF21 suppressed the induced expression of CHOP and DR5 in THP1 macrophage derived foam cells.

Conclusion: FGF21 protects against the formation and apoptosis of THP1 macrophages derived foam cells through suppressing the expression of CHOP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Fibroblast Growth Factors / pharmacology*
  • Foam Cells / drug effects
  • Foam Cells / metabolism*
  • Gene Expression Regulation
  • Humans
  • Lipoproteins, LDL / toxicity*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Transcription Factor CHOP / antagonists & inhibitors*
  • Transcription Factor CHOP / biosynthesis*

Substances

  • DDIT3 protein, human
  • Lipoproteins, LDL
  • fibroblast growth factor 21
  • oxidized low density lipoprotein
  • Transcription Factor CHOP
  • Fibroblast Growth Factors