Regulatory T cells ameliorate hyperhomocysteinaemia-accelerated atherosclerosis in apoE-/- mice
Regulatory T cells ameliorate hyperhomocysteinaemia-accelerated atherosclerosis in apoE-/- mice
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调节性 T 细胞改善 apoE-/- 小鼠高同型半胱氨酸血症加速的动脉粥样硬化
DOI：
10.1093/cvr/cvp182
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发表时间：
2009-10-01
影响因子：
10.8
通讯作者：
Wang, Xian
中科院分区：
文献类型：
--
作者：
Feng, Juan;Zhang, Zhenmin;Wang, Xian
动脉粥样硬化是一种炎症性疾病，T细胞驱动的免疫炎症反应有助于疾病的发生和进展。我们在apoE-/-小鼠中研究了调节性T细胞（TCFs）在高同型半胱氨酸（HHcy）加速动脉粥样硬化中的潜在作用。apoE-/-小鼠被喂食正常小鼠食物，在饮用水中补充或不补充高水平的同型半胱氨酸（Hcy）（1.8 g/L），持续2、4和6周。在HHcy apoE-/-小鼠中，动脉粥样硬化病变面积在2周时略有增加，在4周和6周时显著升高。共转移正常TcB可显著减少动脉粥样硬化病变的大小和T细胞和巨噬细胞向斑块中的浸润。此外，Treg共转移逆转了HHcy加速的T细胞增殖，-增加了促炎性，-减少了活化脾T细胞的抗炎细胞因子分泌。在临床相关的血浆Hcy水平下，HHcy apoE-/-小鼠中脾脏T细胞中的T细胞比例和抑制活性降低，这与Foxp 3的mRNA和蛋白表达降低有关，Foxp 3是一种控制小鼠Treg发育和功能的因子。此外，Hcy在体外可显著降低Tcl 3的比例和抑制作用，HHcy抑制Tcl 3的功能，可能是Hcy加速apoE-/-小鼠动脉粥样硬化的机制之一。
Atherosclerosis is an inflammatory disease with T cell-driven immunoinflammatory responses contributing to disease initiation and progression. We investigated the potential role of regulatory T cells (Tregs) in hyperhomocysteinaemia (HHcy)-accelerated atherosclerosis in apoE-/- mice.apoE-/- mice were fed normal mouse chow supplemented with or without a high level of homocysteine (Hcy) (1.8 g/L) in drinking water for 2, 4, and 6 weeks. Atherosclerotic lesion area was slightly increased at 2 weeks and substantially elevated at 4 and 6 weeks in HHcy apoE-/- mice. Cotransfer of normal Tregs significantly attenuated atherosclerotic lesion size and infiltration of T cells and macrophages into plaque. Furthermore, Treg cotransfer reversed HHcy-accelerated proliferation of T cells, -increased pro-inflammatory, and -decreased anti-inflammatory cytokine secretion from activated splenic T cells. With a clinically relevant level of plasma Hcy, the proportion of Tregs and suppressive activity in splenic T cells were reduced in HHcy apoE-/- mice, which was associated with reduced mRNA and protein expression of Foxp3, a factor governing mouse Treg development and function. In addition, Hcy significantly attenuated the proportion and suppressive effects of Tregs in vitro.HHcy suppresses the function of Tregs, which may be responsible for HHcy-accelerated atherosclerosis in apoE-/- mice.