Synthetic retinoid Am80 reduces scavenger receptor expression and atherosclerosis in mice by inhibiting IL-6
Synthetic retinoid Am80 reduces scavenger receptor expression and atherosclerosis in mice by inhibiting IL-6
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DOI：
10.1161/01.atv.0000214296.94849.1c
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发表时间：
2006-05-01
影响因子：
8.7
通讯作者：
Nagai, R
中科院分区：
文献类型：
--
作者：
Takeda, N;Manabe, I;Nagai, R
背景-巨噬细胞清道夫受体促进修饰的低密度脂蛋白(LDL)的摄取、泡沫细胞的形成和动脉粥样硬化的发展。鉴于包括IL-6在内的促炎细胞因子可以调节巨噬细胞的泡沫形成过程，本研究的目的是确定合成的维甲酸受体-α/β受体特异性激动剂AM80是否可以调节巨噬细胞的脂质堆积和泡沫细胞的形成。方法和结果-AM80抑制12-肉豆蔻酸酯13-乙酸酯(PMA)或血管紧张素II诱导的小鼠Raw264巨噬细胞产生IL-6。它还通过抑制IL-6抑制两种主要清道夫受体(清道夫受体A[SR-A]和CD36)的表达，并抑制巨噬细胞泡沫细胞的形成。全身应用Am80可减少载脂蛋白E(ApoE)缺陷小鼠的动脉粥样硬化病变面积和泡沫细胞积聚，降低血清IL-6和IL-1β浓度，而不影响体重、血脂和IL-10水平。结论Am80体外抑制apoE缺陷小鼠的清道夫受体表达和巨噬细胞泡沫细胞的形成，防止体内动脉粥样硬化的形成。这表明AM80是一种新的候选药物，在预防和治疗动脉粥样硬化方面可能非常有用。
Background - Macrophage scavenger receptors facilitate the uptake of modified low-density lipoprotein (LDL), formation of foam cells, and development of atherosclerosis. Given that proinflammatory cytokines, including IL-6, can modulate the macrophage foaming process, the aim of the present study was to determine whether the synthetic retinoic acid receptor-alpha/beta-specific agonist Am80, which is also an IL-6 inhibitor, can modulate macrophage lipid accumulation and foam cell formation.Methods and Results - Am80 suppressed IL-6 production induced by 12-myristate13-acetate (PMA) or angiotensin II in mouse Raw264 macrophages. It also suppressed expression of the 2 major scavenger receptors ( scavenger receptor-A [SR-A] and CD36), in part by inhibiting IL-6, and inhibited macrophage foam cell formation. Systemic administration of Am80 led to reductions in the areas of atherosclerotic lesions and foam cell accumulation in the aortas of apolipoprotein E ( apoE)- deficient mice and reduced serum concentrations of IL-6 and IL-1 beta without affecting body weights, serum lipid profiles or IL-10 levels.Conclusions - Am80 suppresses scavenger receptor expression and macrophage foam cell formation in vitro and prevents atherogenesis in apoE-deficient mice in vivo. This suggests Am80 is a novel candidate agent that could be highly useful in the prevention and treatment of atherosclerosis.