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Recently, it has been reported that some calcium–channel blockers (CCB) reduced atherosclerosis with anti–inflammatory or anti–atherosclerotic effects in vivo. It is well known that monocytes or macrophages play important roles in atherosclerosis. However, the effects of CCB on macrophage activation remain unclear. The aim of the current study was to evaluate the effects of azelnidipine, a dihydropyridine L–type calcium channel, on the activation of macrophages and to elucidate precise mechanisms of CCB for atherosclerosis.
Methods and Results
THP–1 monocytes, human leukemic cell line, were stimulated with 10 ng/ml of phorbor myristate acetate (PMA) one hour after the pretreatment with 10 μM of azelnidipine or DMSO and harvested 48 or 72 hours after the intervention. Azelnidipine blocked the expression of adhesion molecule, intercellular Adhesion Molecule–1 (ICAM–1) by FACS analysis. ApoE and MMP9 which indicate as markers for macrophage differentiation were inhibited with azelnidipine evaluated by quantitative RT–PCR. The level of LOX–1 mRNA, a scavenger receptor, was also reduced significantly by pretreatment of 10 uM azelnidipine. Azelnidipine also lowered the uptake of DiI–ac–LDL (acetylated LDL). Although L–type calcium channel, Cav1.2, expressed 10–fold higher after PMA stimulation for 24 hours, knockdown of CACNA1C gene, which encodes Cav1.2 protein in human, with siRNA could not inhibit macrophage activation. Therefore, these effects of azelnidipine on the macrophage differentiation were independent of CACNA1C gene.
These results suggest that azelnidipine have the potent anti–atherosclerotic properties through the inhibition of macrophage activation.
Moderated Poster Contributions
Poster Sessions, Expo North
Saturday, March 09, 2013, 10:00 a.m.–10:45 a.m.
Session Title: Vascular Medicine Basic: Atherogenesis
Abstract Category: 33. Vascular Medicine: Basic
Presentation Number: 1125M–169
- 2013 American College of Cardiology Foundation