Atorvastatin improves plaque stability in ApoE-knockout mice by regulating chemokines and chemokine receptors.
Atorvastatin improves plaque stability in ApoE-knockout mice by regulating chemokines and chemokine receptors.
复制标题
阿托伐他汀通过调节趋化因子和趋化因子受体改善 ApoE 敲除小鼠的斑块稳定性
DOI：
10.1371/journal.pone.0097009
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
He B
中科院分区：
文献类型：
--
作者：
Nie P;Li D;Hu L;Jin S;Yu Y;Cai Z;Shao Q;Shen J;Yi J;Xiao H;Shen L;He B
有据可查的是，他汀类药物在冠状动脉动脉中保护动脉粥样硬化的变化和斑块的不稳定性，但使用先前建立的小鼠模型来了解弱点的动脉。但是，在此剂量下；与对照组相比，在阿托养蛋白处理的组中，它们显着降低了。船壁，我们推测阿托伐他蛋白可能是由于单核细胞募集到原始实验的一部分。 Asma炎症标记C反应蛋白（CRP）和肿瘤坏死在阿托伐他蛋白处理的小鼠中，α也显着降低，我们的结果表明，阿特伐他蛋白可以改善与血浆胆固醇水平无关的小鼠的斑块稳定性他汀类药物的另一种动脉保护机制。
It is well documented that statins protect atherosclerotic patients from inflammatory changes and plaque instability in coronary arteries. However, the underlying mechanisms are not fully understood. Using a previously established mouse model for vulnerable atherosclerotic plaque, we investigated the effect of atorvastatin (10 mg/kg/day) on plaque morphology. Atorvastatin did not lower plasma total cholesterol levels or affect plaque progression at this dosage; however, vulnerable plaque numbers were significantly reduced in the atorvastatin-treated group compared to control. Detailed examinations revealed that atorvastatin significantly decreased macrophage infiltration and subendothelial lipid deposition, reduced intimal collagen content, and elevated collagenase activity and expression of matrix metalloproteinases (MMPs). Because vascular inflammation is largely driven by changes in monocyte/macrophage numbers in the vessel wall, we speculated that the anti-inflammatory effect of atorvastatin may partially result from decreased monocyte recruitment to the endothelium. Further experiments showed that atorvastatin downregulated expression of the chemokines monocyte chemoattractant protein (MCP)-1, chemokine (C-X3-C motif) ligand 1 (CX3CL1) and their receptors CCR2 and, CX3CR1, which are mainly responsible for monocyte recruitment. In addition, levels of the plasma inflammatory markers C-reactive protein (CRP) and tumor necrosis factor (TNF)-α were also significantly decrease in atorvastatin-treated mice. Collectively, our results demonstrate that atorvastatin can improve plaque stability in mice independent of plasma cholesterol levels. Given the profound inhibition of macrophage infiltration into atherosclerotic plaques, we propose that statins may partly exert protective effects by modulating levels of chemokines and their receptors. These findings elucidate yet another atheroprotective mechanism of statins.
登录
查看更多内容
影响因子：
11.1
作者：
Soehnlein, Oliver;Drechsler, Maik;Doering, Yvonne;Lievens, Dirk;Hartwig, Helene;Kemmerich, Klaus;Ortega-Gomez, Almudena;Mandl, Manuela;Vijayan, Santosh;Projahn, Delia;Garlichs, Christoph D.;Koenen, Rory R.;Hristov, Mihail;Lutgens, Esther;Zernecke, Alma;Weber, Christian
通讯作者：
Weber, Christian
DOI：
10.1161/atvbaha.111.237412
发表时间：
2012-03-01
影响因子：
8.7
作者：
White, Gemma E.;Greaves, David R.
通讯作者：
Greaves, David R.
影响因子：
5.7
作者：
Naert, Gaelle;Rivest, Serge
通讯作者：
Rivest, Serge
影响因子：
5.8
作者：
Ruiz-Velasco, N;Domínguez, A;Vega, MA
通讯作者：
Vega, MA
影响因子：
15.9
作者：
Martin, G;Duez, H;Staels, B
通讯作者：
Staels, B