PMID- 12954370 OWN - NLM STAT- MEDLINE DCOM- 20040503 LR - 20190624 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 475 IP - 1-3 DP - 2003 Aug 15 TI - Dilazep and fenofibric acid inhibit MCP-1 mRNA expression in glycoxidized LDL-stimulated human endothelial cells. PG - 139-47 AB - 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. FAU - Sonoki, Kazuo AU - Sonoki K AD - Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Iwase, Masanori AU - Iwase M FAU - Iino, Kenzo AU - Iino K FAU - Ichikawa, Kojiro AU - Ichikawa K FAU - Yoshinari, Mototaka AU - Yoshinari M FAU - Ohdo, Shigehiro AU - Ohdo S FAU - Higuchi, Shun AU - Higuchi S FAU - Iida, Mitsuo AU - Iida M LA - eng PT - Journal Article PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Chemokine CCL2) RN - 0 (Cholesterol, LDL) RN - 0 (Glycolates) RN - 0 (RNA, Messenger) RN - 0WT12SX38S (glycolic acid) RN - BGF9MN2HU1 (fenofibric acid) RN - F8KLC2BD5Z (Dilazep) RN - U202363UOS (Fenofibrate) SB - IM MH - Cells, Cultured MH - Chemokine CCL2/*antagonists & inhibitors/biosynthesis/genetics MH - Cholesterol, LDL/*pharmacology MH - Dilazep/*pharmacology MH - Dose-Response Relationship, Drug MH - Endothelial Cells/*drug effects/metabolism MH - Endothelium, Vascular/drug effects/metabolism MH - Fenofibrate/*analogs & derivatives/*pharmacology MH - Gene Expression Regulation/drug effects/physiology MH - Glycolates/pharmacology MH - Humans MH - RNA, Messenger/*antagonists & inhibitors/biosynthesis/genetics EDAT- 2003/09/05 05:00 MHDA- 2004/05/05 05:00 CRDT- 2003/09/05 05:00 PHST- 2003/09/05 05:00 [pubmed] PHST- 2004/05/05 05:00 [medline] PHST- 2003/09/05 05:00 [entrez] AID - S0014299903021095 [pii] AID - 10.1016/s0014-2999(03)02109-5 [doi] PST - ppublish SO - Eur J Pharmacol. 2003 Aug 15;475(1-3):139-47. doi: 10.1016/s0014-2999(03)02109-5.