日本語フィールド
著者：*Komoda H, Shiraki A, Oyama JI, Nishikido T, Node K.題名：Azelnidipine Inhibits the Differentiation and Activation of THP-1 Macrophages through the L-Type Calcium Channel.発表情報：J Atheroscler Thromb. 巻: 25 号: 8 ページ: 690-697キーワード：概要：Aim: Recently, calcium channel blockers (CCBs) have been reported to reduce atherosclerosis with anti-inflammatory or antiatherosclerotic effects in vivo. It is well established that monocytes and macrophages play important roles in promoting atherosclerosis. However, the effects of CCBs on macrophage activation remain unclear. The aim of this study was to evaluate the effects of azelnidipine, a dihydropyridine L-type CCB, on the activation of macrophages and to clarify the mechanisms of the effects of CCBs on atherosclerosis.
Methods: THP-1 monocytes, a human leukemic cell line, were stimulated with 50 ng/mL of phorbol-12-myristate-13-acetate (PMA) 1 h after pretreatment with 10 μM azelnidipine or dimethyl sulfoxide (DMSO), and harvested.
Results: Azelnidipine blocked the expression of intercellular adhesion molecule-1 quantified by FACS analysis. The expression levels of Apo E and MMP9, which are markers of macrophage differentiation, were inhibited by azelnidipine as evaluated by quantitative RT-PCR. The level of LOX-1 mRNA, a scavenger receptor, was also reduced significantly by pretreatment with 10 μM azelnidipine. Azelnidipine also lowered the uptake of acetylated LDL. The expression of the L-type calcium channel Cav1.2 was 10-fold higher after 24 h of PMA stimulation. A knockdown of the CACNA1C gene, which encodes Cav1.2 protein in humans, with siRNA blocked the effect of reducing adhesion by azelnidipine, indicating that the effects of azelnidipine on macrophage differentiation were expressed through the CACNA1C gene.
Conclusion: Our results suggest that azelnidipine has potent antiatherosclerotic properties by inhibition of macrophage activation through Cav1.2.抄録：英語フィールド
Author：*Komoda H, Shiraki A, Oyama JI, Nishikido T, Node K.Title：Azelnidipine Inhibits the Differentiation and Activation of THP-1 Macrophages through the L-Type Calcium Channel.Announcement information:J Atheroscler Thromb. Vol: 25 Issue: 8 Page: 690-697An abstract：Aim: Recently, calcium channel blockers (CCBs) have been reported to reduce atherosclerosis with anti-inflammatory or antiatherosclerotic effects in vivo. It is well established that monocytes and macrophages play important roles in promoting atherosclerosis. However, the effects of CCBs on macrophage activation remain unclear. The aim of this study was to evaluate the effects of azelnidipine, a dihydropyridine L-type CCB, on the activation of macrophages and to clarify the mechanisms of the effects of CCBs on atherosclerosis.
Methods: THP-1 monocytes, a human leukemic cell line, were stimulated with 50 ng/mL of phorbol-12-myristate-13-acetate (PMA) 1 h after pretreatment with 10 μM azelnidipine or dimethyl sulfoxide (DMSO), and harvested.
Results: Azelnidipine blocked the expression of intercellular adhesion molecule-1 quantified by FACS analysis. The expression levels of Apo E and MMP9, which are markers of macrophage differentiation, were inhibited by azelnidipine as evaluated by quantitative RT-PCR. The level of LOX-1 mRNA, a scavenger receptor, was also reduced significantly by pretreatment with 10 μM azelnidipine. Azelnidipine also lowered the uptake of acetylated LDL. The expression of the L-type calcium channel Cav1.2 was 10-fold higher after 24 h of PMA stimulation. A knockdown of the CACNA1C gene, which encodes Cav1.2 protein in humans, with siRNA blocked the effect of reducing adhesion by azelnidipine, indicating that the effects of azelnidipine on macrophage differentiation were expressed through the CACNA1C gene.
Conclusion: Our results suggest that azelnidipine has potent antiatherosclerotic properties by inhibition of macrophage activation through Cav1.2.