Dilazep and fenofibric acid inhibit MCP-1 mRNA expression in glycoxidized LDL-stimulated human endothelial cells.
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.
Sonoki
Kazuo
K
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
Iwase
Masanori
M
Iino
Kenzo
K
Ichikawa
Kojiro
K
Yoshinari
Mototaka
M
Ohdo
Shigehiro
S
Higuchi
Shun
S
Iida
Mitsuo
M
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D008078:Cholesterol, LDL / Q000494:pharmacology*; D004109:Dilazep / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006016:Glycolates / Q000494:pharmacology; D006801:Humans; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
D018932:Chemokine CCL2; D008078:Cholesterol, LDL; D006016:Glycolates; D012333:RNA, Messenger; C031149:glycolic acid; C006012:fenofibric acid; D004109:Dilazep; D011345:Fenofibrate