CLI-095 decreases atherosclerosis by modulating foam cell formation in apolipoprotein E-deficient mice.
CLI-095 decreases atherosclerosis by modulating foam cell formation in apolipoprotein E-deficient mice.
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DOI：
10.3892/mmr.2016.5233
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发表时间：
2016-07
影响因子：
3.4
通讯作者：
Qu P
中科院分区：
文献类型：
--
作者：
Wang XQ;Wan HQ;Wei XJ;Zhang Y;Qu P
toll样受体4 （TLR4）被认为在动脉粥样硬化易感小鼠动脉粥样硬化的发生和发展中起关键作用；然而，TLR4抑制剂治疗是否能减轻动脉粥样硬化仍不确定。本研究旨在确定TLR4抑制剂CLI-095对载脂蛋白e缺陷（ApoE−/−）小鼠的血管保护作用。ApoE−/−小鼠分别饲喂鼠粮或高脂饲料，并分别给予或不给予CLI-095治疗10周。cli -095处理小鼠主动脉段动脉粥样硬化斑块平均面积比载药处理小鼠小54.3% （P=0.0051）。在体外，用或不加CLI-095处理小鼠腹腔巨噬细胞，随后用氧化低密度脂蛋白刺激。CLI-095显著降低凝集素样氧化低密度脂蛋白受体-1和酰基辅酶A：胆固醇酰基转移酶-1的表达水平，并显著上调atp结合盒转运蛋白A1的表达水平，主要是通过抑制TLR4/核因子-κB信号通路的激活。本研究结果表明，在体内模型中，TLR4抑制剂CLI-095通过减少巨噬细胞泡沫细胞的形成，具有抑制动脉粥样硬化进展的能力。
Toll-like receptor 4 (TLR4) is considered to have a critical role in the occurrence and development of atherosclerosis in atherosclerosis-prone mice; however, it remains uncertain whether treatment with a TLR4 inhibitor may attenuate atherosclerosis. The present study aimed to determine the vascular protective effects of the TLR4 inhibitor CLI-095 on apolipoprotein E-deficient (ApoE−/−) mice. ApoE−/− mice were fed either chow or a high-fat diet, and were treated with or without CLI-095 for 10 weeks. The mean atherosclerotic plaque area in the aortic sections of CLI-095-treated mice was 54.3% smaller than in the vehicle-treated mice (P=0.0051). In vitro, murine peritoneal macrophages were treated with or without CLI-095, and were subsequently stimulated with oxidized low-density lipoprotein. Treatment with CLI-095 markedly reduced the expression levels of lectin-like oxidized low-density lipoprotein receptor-1 and acyl-coenzyme A:cholesterol acyltransferase-1, and significantly upregulated the expression levels of ATP-binding cassette transporter A1, predominantly via suppressing activation of the TLR4/nuclear factor-κB signaling pathway. The results of the present study indicated that the TLR4 inhibitor CLI-095 has the ability to suppress the progression of atherosclerosis in an in vivo model by reducing macrophage foam cell formation.