Deficiency in lymphotoxin β receptor protects from atherosclerosis in apoE-deficient mice

Circulation Research
Maria GrandochJens W Fischer

Abstract

Lymphotoxin β receptor (LTbR) regulates immune cell trafficking and communication in inflammatory diseases. However, the role of LTbR in atherosclerosis is still unclear. The aim of this study was to elucidate the role of LTbR in atherosclerosis. After 15 weeks of feeding a Western-type diet, mice double-deficient in apolipoprotein E and LTbR (apoE(-/-)/LTbR(-/-)) exhibited lower aortic plaque burden than did apoE(-/-) littermates. Macrophage content at the aortic root and in the aorta was reduced, as determined by immunohistochemistry and flow cytometry. In line with a decrease in plaque inflammation, chemokine (C-C motif) ligand 5 (Ccl5) and other chemokines were transcriptionally downregulated in aortic tissue from apoE(-/-)/LTbR(-/-) mice. Moreover, bone marrow chimeras demonstrated that LTbR deficiency in hematopoietic cells mediated the atheroprotection. Furthermore, during atheroprogression, apoE(-/-) mice exhibited increased concentrations of cytokines, for example, Ccl5, whereas apoE(-/-)/LTbR(-/-) mice did not. Despite this decreased plaque macrophage content, flow cytometric analysis showed that the numbers of circulating lymphocyte antigen 6C (Ly6C)(low) monocytes were markedly elevated in apoE(-/-)/LTbR(-/-) mice. ...Continue Reading

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Citations

May 14, 2016·Thrombosis and Haemostasis·Irene Andrés-BlascoHerminia González-Navarro
Jun 18, 2016·Frontiers in Immunology·Klaus LeyJenny P Ting
Dec 21, 2017·Disease Markers·Lili JiangLongxian Cheng
Jun 23, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Ellen Rouwet, Esther Lutgens
Apr 1, 2015·Molecular and Cellular Biology·Chaowei WuMichael J Garabedian
Jun 27, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Lu XuHuaizhu Wu
Feb 17, 2019·Nature Reviews. Cardiology·Karin H SimonsPaul H A Quax
Jun 6, 2019·Frontiers in Immunology·Desheng HuSarajo K Mohanta

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