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

• Published in: Cardiovascular research Vol. 84; no. 1; pp. 155 - 163
• Main Authors: Feng, Juan, Zhang, Zhenmin, Kong, Wei, Liu, Bo, Xu, Qingbo, Wang, Xian
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.10.2009
• Subjects: Adoptive Transfer; Animals; Apolipoproteins E - physiology; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - etiology; Atherosclerosis - prevention & control; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cells, Cultured; Cytokines - biosynthesis; Female; Forkhead Transcription Factors - analysis; Forkhead Transcription Factors - genetics; Hyperhomocysteinaemia; Hyperhomocysteinemia - complications; Immunoinflammatory diseases; Interleukin-10 - physiology; Lymphocyte Activation; Medical sciences; Mice; Mice, Inbred C57BL; Regulatory T cells; RNA, Messenger - analysis; T lymphocytes; T-Lymphocytes, Regulatory - physiology; Transforming Growth Factor beta - physiology; T lymphocytes; Immunoinflammatory diseases; Hyperhomocysteinaemia; Regulatory T cells; Atherosclerosis; Disease; Rodentia; Cardiovascular disease; Phlebology; Vascular disease; Vertebrata; Mammalia; Mouse; Immunological investigation; Animal; T-Lymphocyte; Hyperhomocysteinemia; Circulatory system; Cardiology
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvp182

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.