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

Kazuo Sonoki, Masanori Iwase, Kenzo Iino, Kojiro Ichikawa, Mototaka Yoshinari, Shigehiro Ohdo, Shun Higuchi, Mitsuo Iida

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14 Citations (Scopus)

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-κB). 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 μg/ml dilazep and 100 μM fenofibric acid abrogated MCP-1 mRNA expression. ZM241385, an A2a adenosine receptor antagonist, partially inhibited the suppressive effect of dilazep. NF-κB activity was also suppressed by 1 μg/ml dilazep and 10 μM 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.

Original languageEnglish
Pages (from-to)139-147
Number of pages9
JournalEuropean Journal of Pharmacology
Volume475
Issue number1-3
DOIs
Publication statusPublished - Aug 15 2003

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All Science Journal Classification (ASJC) codes

  • Pharmacology

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