TY - JOUR
T1 - Dilazep and fenofibric acid inhibit MCP-1 mRNA expression in glycoxidized LDL-stimulated human endothelial cells
AU - Sonoki, Kazuo
AU - Iwase, Masanori
AU - Iino, Kenzo
AU - Ichikawa, Kojiro
AU - Yoshinari, Mototaka
AU - Ohdo, Shigehiro
AU - Higuchi, Shun
AU - Iida, Mitsuo
PY - 2003/8/15
Y1 - 2003/8/15
N2 - 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.
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-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.
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U2 - 10.1016/S0014-2999(03)02109-5
DO - 10.1016/S0014-2999(03)02109-5
M3 - Article
C2 - 12954370
AN - SCOPUS:0042381862
VL - 475
SP - 139
EP - 147
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -