The macrophage C-type lectin receptor CLEC5A (MDL-1) expression is associated with early plaque progression and promotes macrophage survival

Journal of Translational Medicine

Research

Gang Gu¹  Weixin Xiong¹  Rong Tao¹  Rui Xi¹  Fang Wang¹  Lin Lu²  Haibo Wang³ 

[1] Department of Cardiology, Ruijin Hospital, Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Huangpu District, 200025, Shanghai, China;Department of Cardiology, Ruijin Hospital, Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Huangpu District, 200025, Shanghai, China;Institute of Cardiovascular Disease, Jiao Tong University School of Medicine, 200025, Shanghai, China;Institute of Cardiovascular Disease, Jiao Tong University School of Medicine, 200025, Shanghai, China;

关键词: Atherosclerosis;    Plaque progression;    Macrophage;    Apoptosis;    Myeloid DAP12-associating lectin-1;   

DOI  :  10.1186/s12967-017-1336-z

 received in 2017-08-18, accepted in 2017-10-30,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundBiomarkers of early plaque progression are still elusive. Myeloid DAP12-associating lectin-1 (MDL-1), also called CLEC5A, is a C-type lectin receptor implicated in the progression of multiple acute and chronic inflammatory diseases. However, the relationship between its level and atherosclerosis is unknown. In this study, we aimed to investigate the correlation between macrophage MDL-1 expression and early atherosclerosis progression.MethodsImmunofluorescence staining, real-time PCR and western blot were performed to analyze MDL-1 expression in aorta or mice macrophages. The role of MDL-1 in macrophage survival was further investigated by adenovirus infection and TUNEL assay.ResultsSignificant MDL-1 expression was found in advanced human and apoE−/− mice atherosclerotic plaques, especially in lesional macrophages. In the model of atherosclerosis regression, we found MDL-1 expression was highly downregulated in lesional macrophages from ldlr−/− mouse regressive plaques, coincident with a reduction in lesional macrophage content and marker of M1 proinflammatory macrophages. Furthermore, we found MDL-1 was significantly expressed in inflammatory M1 subtype polarized bone marrow-derived macrophages. In vitro experiments, the level of MDL-1 was remarkably elevated in macrophages treated with pathophysiological drivers of plaque progression, such as oxidized low-density lipoprotein (ox-LDL) and hypoxia. Mechanistically, we demonstrated that MDL-1 overexpression notably promoted macrophage survival and decreased cleaved caspase-3 expression under ox-LDL stimulation, which suggested that it could maintain lesional macrophage survival and cause its accumulation.ConclusionsThis study firstly demonstrated that MDL-1 is mainly expressed in atherosclerotic lesional macrophages and increased macrophage MDL-1 expression is associated with early plaque progression and promotes macrophage survival.

【 授权许可】

CC BY   
© The Author(s) 2017