Feng Juan, Zhang Zhenmin, Kong Wei, Liu Bo, Xu Qingbo, Wang Xian
Department of Physiology and Pathophysiology, School of Basic Medical Science, Peking University, Beijing 100191, PR China.
Cardiovasc Res. 2009 Oct 1;84(1):155-63. doi: 10.1093/cvr/cvp182. Epub 2009 Jun 5.
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.
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参与疾病的发生和发展。我们研究了调节性T细胞（Tregs）在载脂蛋白E基因敲除（apoE-/-）小鼠高同型半胱氨酸血症（HHcy）加速动脉粥样硬化中的潜在作用。
给apoE-/-小鼠喂食正常小鼠饲料，饮水中添加或不添加高水平同型半胱氨酸（Hcy）（1.8 g/L），持续2、4和6周。HHcy apoE-/-小鼠在2周时动脉粥样硬化病变面积略有增加，在4周和6周时显著升高。共转移正常Tregs可显著减小动脉粥样硬化病变大小，并减少T细胞和巨噬细胞向斑块内的浸润。此外，Treg共转移逆转了HHcy加速的T细胞增殖、增加的促炎细胞因子分泌以及活化脾T细胞抗炎细胞因子分泌的减少。在具有临床相关水平的血浆Hcy时，HHcy apoE-/-小鼠脾T细胞中Tregs的比例和抑制活性降低，这与调节小鼠Treg发育和功能的因子Foxp3的mRNA和蛋白表达降低有关。此外，Hcy在体外显著减弱了Tregs的比例和抑制作用。
HHcy抑制Tregs的功能，这可能是HHcy加速apoE-/-小鼠动脉粥样硬化的原因。
