Combinatorial interference of toll-like receptor 2 and 4 synergistically stabilizes atherosclerotic plaque in apolipoprotein E-knockout mice.
Combinatorial interference of toll-like receptor 2 and 4 synergistically stabilizes atherosclerotic plaque in apolipoprotein E-knockout mice.
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Toll样受体2和4的组合干扰可协同稳定载脂蛋白E敲除小鼠的动脉粥样硬化斑块
DOI：
10.1111/j.1582-4934.2010.01028.x
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发表时间：
2011-03
影响因子：
5.3
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Yang JM;Wang Y;Qi LH;Wang Y;Gao F;Ding SF;Ni M;Liu CX;Zhang C;Zhang Y
为了验证联合干扰toll样受体2 （TLR2）和TLR4在稳定动脉粥样硬化斑块方面优于单独干扰TLR2或TLR4的假设，我们构建了携带TLR2或TLR4小干扰RNA的慢病毒，并在体外实验中证明其可显著降低TLR2或TLR4 mRNA和蛋白的表达。将150只饲喂高脂饲料的载脂蛋白E - / -小鼠分为对照组、模拟组、TLR2i组、TLR4i组和TLR2 + 4i组，在小鼠颈动脉周围围上收缩项圈诱导斑块形成。TLR2i和TLR4i病毒悬液分别转染到颈动脉斑块中，TLR2i和TLR4i亚组或TLR2 + 4i亚组联合转染。慢病毒转染4周后，颈动脉斑块中TLR2或TLR4 mRNA和蛋白表达明显减弱，导致局部炎性细胞因子表达减少，斑块中脂质和巨噬细胞含量降低，斑块中胶原蛋白含量增加，斑块易损指数降低。因子方差分析显示，TLR4i和TLR2i在稳定斑块方面存在协同作用。综上所述，联合干预TLR2和TLR4比单独干预TLR2或TLR4更有效地减少局部炎症和稳定斑块。
To test the hypothesis that combinatorial interference of toll-like receptor 2 (TLR2) and TLR4 is superior to isolated interference of TLR2 or TLR4 in stabilizing atherosclerotic plaques, lentiviruses carrying small interfering RNA of TLR2 or TLR4 were constructed and proved efficacious for knocking down mRNA and protein expression of TLR2 or TLR4 significantly in vitro. One hundred and fifty apolipoprotein E−/− mice fed a high-fat diet were divided into the control, mock, TLR2i, TLR4i and TLR2 + 4i subgroups and a constrictive collar was placed around carotid artery of these mice to induce plaque formation. TLR2i and TLR4i viral suspension was transfected into carotid plaques, respectively, in TLR2i and TLR4i subgroups, or in combination in TLR2 + 4i subgroup. Four weeks after lentivirus transfection, mRNA and protein expression of TLR2 or TLR4 was attenuated markedly in carotid plaques, leading to reduced local inflammatory cytokine expression and plaque content of lipid and macrophages, increased plaque content of collagen and lowered plaque vulnerability index. Factorial ANOVA analysis revealed that there was a synergistic effect between TLR4i and TLR2i in stabilizing plaques. In conclusion, combinatorial interference of TLR2 and TLR4 reduces local inflammation and stabilizes plaques more effectively than interference of TLR2 or TLR4 alone.
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影响因子：
3.6
作者：
Yamamoto, M;Takeda, K;Akira, S
通讯作者：
Akira, S
影响因子：
37.8
作者：
von der Thüsen, JH;van Berkel, TJC;Biessen, EAL
通讯作者：
Biessen, EAL
影响因子：
3.3
作者：
Martinovic, I;Abegunewardene, N;Lindemann, S
通讯作者：
Lindemann, S
影响因子：
4.4
作者：
Faure, E;Thomas, L;Arditi, M
通讯作者：
Arditi, M
慢病毒介导的siRNA用于抗病毒疗法的递送。
影响因子：
5.1
作者：
Morris KV;Rossi JJ
通讯作者：
Rossi JJ