Azelnidipine, a new long-acting calcium-channel blocker, inhibits tumour necrosis factor-alpha-induced monocyte chemoattractant protein-1 expression in endothelial cells.
Dihydropyridine-based calcium antagonists are among the most widely used drugs for the treatment of hypertension. Since azelnidipine is a highly lipid-soluble dihydropyridine-based calcium antagonist with high vascular affinity, it is conceivable that azelnidipine could play a protective role against atherosclerosis. The aim of this study was to determine whether azelnidipine could suppress the expression of monocyte chemoattractant protein-1, a principal chemokine which mediates the recruitment of monocytes to the vasculature, in tumour necrosis factor (TNF)-alpha-exposed human umbilical vein endothelial cells. TNF-alpha, at a concentration of 10 ng/ml, upregulated monocyte chemoattractant protein-1 mRNA levels about seven-fold. Azelnidipine, 10 nmol/l, was found to inhibit the TNF-alpha-induced upregulation of monocyte chemoattractant protein-1 mRNA levels in human umbilical vein endothelial cells significantly. Furthermore, azelnidipine suppressed TNF-alpha-induced monocyte chemoattractant protein-1 production by human umbilical vein endothelial cells. This study demonstrates a novel beneficial aspect of azelnidipine, whereby azelnidipine could play a protective role against atherosclerosis by suppressing monocyte chemoattractant protein-1 overexpression in endothelial cells.
Matsui
T
T
Department of Internal Medicine, Institute for Basic and Clinical Medicine, Kurume University School of Medicine, Kurume, Japan.
Yamagishi
S
S
Nakamura
K
K
Inoue
H
H
D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001483:Base Sequence; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D004095:Dihydropyridines / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C111835:CCL2 protein, human; D002121:Calcium Channel Blockers; D018932:Chemokine CCL2; D017931:DNA Primers; D004095:Dihydropyridines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D001383:Azetidinecarboxylic Acid; C061679:azelnidipine