Abstract
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.
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