Cilostazol inhibits modified low-density lipoprotein uptake and foam cell formation in mouse peritoneal macrophages
Cilostazol inhibits modified low-density lipoprotein uptake and foam cell formation in mouse peritoneal macrophages
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DOI：
10.1016/j.atherosclerosis.2008.10.042
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发表时间：
2009-06-01
期刊：
影响因子：
5.3
通讯作者：
Yabuuchi, Youichi
中科院分区：
文献类型：
--
作者：
Okutsu, Reiko;Yoshikawa, Tomohiro;Yabuuchi, Youichi
修饰的低密度脂蛋白（LDL）通过巨噬细胞清道夫受体（如清道夫受体A和CD 36）的内化被认为在动脉粥样硬化病变的发展中起着至关重要的作用。西洛他唑是一种具有选择性磷酸二酯酶3抑制作用的抗血小板药物，据报道可改善小鼠模型中的动脉粥样硬化。然而，西洛他唑对巨噬细胞中修饰的LDL摄取的影响尚不清楚。因此，我们研究了西洛他唑对小鼠腹腔巨噬细胞（MPM）LDL摄取的影响。西洛他唑显着抑制氧化和乙酰化的LDL摄取MPM，而环AMP（cAMP）-升高剂，db-cAMP和其他磷酸二酯酶3或4抑制剂，不抑制摄取。西洛他唑并不改变MPM中胞浆cAMP水平，蛋白激酶A（PKA）抑制剂并不影响西洛他唑的抑制作用。西洛他唑降低清道夫受体A，但不降低CD 36表达。此外，西洛他唑显著抑制泡沫细胞形成，这表现为酯化胆固醇含量增加。总之，西洛他唑显著抑制小鼠腹腔巨噬细胞中修饰LDL的摄取和泡沫细胞形成，并且西洛他唑的抑制作用可以以cAMP和PKA非依赖性方式诱导。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Internalization of modified low-density lipoprotein (LDL) via macrophage scavenger receptors (e.g. scavenger receptor A and CD36) is thought to play a crucial role in the development of atherosclerotic lesions. Cilostazol, an antiplatelet agent with selective phosphodiesterase 3 inhibitory action, has been reported to ameliorate atherosclerosis in mouse models. However, the effect of cilostazol on modified LDL uptake in macrophages is not known. Thus, we investigated the effect of cilostazol on LDL uptake in mouse peritoneal macrophages (MPM). Cilostazol significantly inhibited oxidized and acetylated LDL uptake in MPM, while cyclic AMP (cAMP)-elevating agents, db-cAMP and other phosphodiesterase 3 or 4 inhibitors, did not inhibit the uptake. Cilostazol did not change cytosolic cAMP levels in MPM, and a protein kinase A (PKA) inhibitor did not influence the inhibitory effects of cilostazol. Cilostazol decreased scavenger receptor A but not CD36 expression. Moreover, cilostazol significantly inhibited foam cell formation, which was represented by an increase in esterified cholesterol content. In conclusion, cilostazol significantly inhibits the uptake of modified LDL and foam cell formation in mouse peritoneal macrophages, and the inhibitory effect of cilostazol can be induced in a cAMP- and PKA-independent manner. (C) 2008 Elsevier Ireland Ltd. All rights reserved.