Dilazep and fenofibric acid inhibit MCP-1 mRNA expression in glycoxidized LDL-stimulated human endothelial cells

Eur J Pharmacol. 2003 Aug 15;475(1-3):139-47. doi: 10.1016/s0014-2999(03)02109-5.

Abstract

We previously reported that glycoxidized low-density lipoprotein (glycoxidized LDL) enhanced monocyte chemoattractant protein-1 (MCP-1) mRNA expression through activation of nuclear factor-kappaB (NF-kappaB). Here we investigated the effects of dilazep, an anti-platelet agent, and fenofibric acid, an active metabolite of fenofibrate, on glycoxidized low-density lipoprotein-(LDL)-enhanced MCP-1 mRNA expression. Both 10 microg/ml dilazep and 100 microM fenofibric acid abrogated MCP-1 mRNA expression. ZM241385, an A2a adenosine receptor antagonist, partially inhibited the suppressive effect of dilazep. NF-kappaB activity was also suppressed by 1 microg/ml dilazep and 10 microM fenofibric acid. The antioxidative activity of these drugs on glycation to native LDL or oxidation to glycated LDL was measured using lipid peroxidation and lyso-phosphatidylcholine contents in LDL. Dilazep but not fenofibric acid exhibited antioxidative activity. Although the mechanisms of anti-atherogenic effects of the two drugs on glycoxidized LDL are different, both dilazep and fenofibric acid could potentially prevent atherosclerosis in diabetes mellitus.

MeSH terms

  • Cells, Cultured
  • Chemokine CCL2 / antagonists & inhibitors*
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / genetics
  • Cholesterol, LDL / pharmacology*
  • Dilazep / pharmacology*
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Fenofibrate / analogs & derivatives*
  • Fenofibrate / pharmacology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Glycolates / pharmacology
  • Humans
  • RNA, Messenger / antagonists & inhibitors*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics

Substances

  • Chemokine CCL2
  • Cholesterol, LDL
  • Glycolates
  • RNA, Messenger
  • glycolic acid
  • fenofibric acid
  • Dilazep
  • Fenofibrate