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Cardiovascular Research Advance Access originally published online on June 5, 2009
Cardiovascular Research 2009 84(1):155-163; doi:10.1093/cvr/cvp182
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Regulatory T cells ameliorate hyperhomocysteinaemia-accelerated atherosclerosis in apoE–/– mice

Juan Feng1,2, Zhenmin Zhang1,2, Wei Kong1,2, Bo Liu1,2, Qingbo Xu3 and Xian Wang1,2,*

1 Department of Physiology and Pathophysiology, School of Basic Medical Science, Peking University, Beijing 100191, PR China
2 Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, PR China
3 Cardiovascular Division, Kings College London BHF Centre, London SE5 9NU, UK

* Corresponding author. Tel/fax: +86 10 82801443. E-mail address: xwang{at}bjmu.edu.cn

Aims: 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.

Methods and results: 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.

Conclusion: HHcy suppresses the function of Tregs, which may be responsible for HHcy-accelerated atherosclerosis in apoE–/– mice.

KEYWORDS Regulatory T cells; Atherosclerosis; Hyperhomocysteinaemia; Immunoinflammatory diseases; T lymphocytes

Time for primary review: 36 days


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