Macrophage-specific overexpression of interleukin-5 attenuates atherosclerosis in LDL receptor-deficient mice
Macrophage-specific overexpression of interleukin-5 attenuates atherosclerosis in LDL receptor-deficient mice
复制标题
巨噬细胞特异性过度表达白细胞介素 5 可减轻 LDL 受体缺陷小鼠的动脉粥样硬化
DOI：
10.1038/gt.2015.33
复制
发表时间：
2015-04
期刊：
影响因子：
5.1
通讯作者：
Ou HL
中科院分区：
文献类型：
--
作者：
Zhao W;Lei TW;Li HM;Sun DQ;Mo XC;Wang ZT;Zhang KL;Ou HL
白细胞介素-5（IL-5）增加天然T15/E06 IgM抗体的分泌，该抗体抑制巨噬细胞摄取氧化低密度脂蛋白（LDL）。本研究旨在确定LDL受体缺陷小鼠（Ldlr−/−）中巨噬细胞特异性表达IL-5是否可以改善胆固醇代谢并减少动脉粥样硬化。为了诱导巨噬细胞特异性IL-5表达，通过骨髓移植将pLVCD 68-IL 5慢病毒递送到Ldlr−/−小鼠中。受体小鼠喂食西式饮食12周以诱导病变形成。我们发现IL-5在pLVCD 68-IL-5转导的骨髓细胞（BMC）的受体中的巨噬细胞中有效且特异性地过表达。与移植了缺乏IL-5编码序列的pLV CD 68的对照小鼠相比，T15/EO 6 IgM抗体的血浆滴度显著升高了58%。与接受pLVCD 68转导的BMCs的小鼠相比，IL-5过表达小鼠的动脉粥样硬化斑块面积减少了43%，并且与主动脉根部病变大小减少2.4倍相关。该研究表明，巨噬细胞特异性IL-5过表达抑制动脉粥样硬化病变的进展。这些发现表明，IL-5细胞因子的表达的调制代表了一个潜在的策略干预家族性高胆固醇血症和其他心血管疾病。
Interleukin-5 (IL-5) increases the secretion of natural T15/EO6 IgM antibodies that inhibit the uptake of oxidized low-density lipoprotein (LDL) by macrophages. This study aimed to determine whether macrophage-specific expression of IL-5 in LDL receptor-deficient mice (Ldlr−/−) could improve cholesterol metabolism and reduce atherosclerosis. To induce macrophage-specific IL-5 expression, the pLVCD68-IL5 lentivirus was delivered into Ldlr−/− mice via bone marrow transplantation. The recipient mice were fed a Western-type diet for 12 weeks to induce lesion formation. We found that IL-5 was efficiently and specifically overexpressed in macrophages in recipients of pLVCD68-IL5-transduced bone marrow cells (BMC). Plasma titers of T15/EO6 IgM antibodies were significantly elevated by 58% compared with control mice transplanted with pLVCD68 lacking the IL-5 coding sequence. Plaque areas of aortas in IL-5-overexpressing mice were reduced by 43% and associated with a 2.4-fold decrease in lesion size at the aortic roots when compared with mice receiving pLVCD68-transduced BMCs. The study showed that macrophage-specific overexpression of IL-5 inhibited the progression of atherosclerotic lesions. These findings suggest that modulation of IL-5 cytokine expression represents a potential strategy for intervention of familial hypercholesterolemia and other cardiovascular diseases.
登录
查看更多内容
影响因子：
5.1
作者：
Bobadilla, S.;Sunseri, N.;Landau, N. R.
通讯作者：
Landau, N. R.
影响因子：
5.4
作者：
Rani, Reena;Smulian, Alan G.;Greaves, David R.;Hogan, Simon P.;Herbert, De'Broski R.
通讯作者：
Herbert, De'Broski R.
影响因子：
3.7
作者：
Sjouke, B;Kusters, D M;Kastelein, J J P;Hovingh, G K
通讯作者：
Hovingh, G K
影响因子：
14.9
作者：
M. C. Huber;U. Jägle;G. Krüger;C. Bonifer
通讯作者：
M. C. Huber;U. Jägle;G. Krüger;C. Bonifer
影响因子：
1.9
作者：
Chien-Da Huang;Chun-Hua Wang;Chien‐Ying Liu;Shu-Min Lin;C. Chou;Wen-Te Liu;Horng-Chyuan Lin;H. Kuo
通讯作者：
Chien-Da Huang;Chun-Hua Wang;Chien‐Ying Liu;Shu-Min Lin;C. Chou;Wen-Te Liu;Horng-Chyuan Lin;H. Kuo