Attenuation of atherosclerotic lesions in diabetic apolipoprotein E‐deficient mice using gene silencing of macrophage migration inhibitory factor

Journal of Cellular and Molecular Medicine

Hui Sun³  XianJun Zhang¹  Lei Zhao³  Xi Zhen³  ShanYing Huang³  ShaSha Wang³  Hong He³  ZiMo Liu³  NaNa Xu³  FaLin Yang²  ZhongHua Qu³  ZhiYong Ma³  Cheng Zhang³  Yun Zhang³ 

[1] Department of Dermatology, Shandong University Qilu Hospital, Jinan, Shandong, China;Department of Clinical Laboratory, Shandong University Qilu Hospital, Jinan, Shandong, China;Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China

关键词: macrophage migration inhibitory factor;    diabetes mellitus;    atherosclerosis;    apolipoprotein E‐deficient mice;    inflammation;   

DOI  :  10.1111/jcmm.12521

来源: Wiley

【 摘 要 】

Abstract

Macrophage migration inhibitory factor (MIF) involves the pathogenesis of atherosclerosis (AS) and increased plasma MIF levels in diabetes mellitus (DM) patients are associated with AS. Here, we have been suggested that MIF could be a critical contributor for the pathological process of diabetes-associated AS by using adenovirus-mediated RNA interference. First, streptozotocin (STZ)-induced diabetic animal model was constructed in 114 apolipoprotein E-deficient mice (apoE−/− mice) fed on a regular chow diet. Then, the animals were randomly divided into three groups: Adenovirus-mediated MIF interference (Ad-MIFi), Ad-enhanced green fluorescent protein (EGFP) and normal saline (NS) group (n ≈ 33/group). Non-diabetic apoE−/− mice (n = 35) were served as controls. Ad-MIFi, Ad-EGFP and NS were, respectively, injected into the tail vein of mice from Ad-MIFi, Ad-EGFP and NS group, which were injected repeatedly 4 weeks later. Physical, biochemical, morphological and molecular parameters were measured. The results showed that diabetic apoE−/− mice had significantly aggravated atherosclerotic lesions. MIF gene interference attenuated atherosclerotic lesions and stabilized atheromatous plaque, accompanied by the decreased macrophages and lipids deposition and inflammatory cytokines production, improved glucose intolerance and plasma cholesterol level, the decreased ratio of matrix matalloproteinase-2/tissue inhibitor of metalloproteinase-1 and plaque instability index. An increased expression of MIF and its ligand CD74 was also detected in the diabetic patients with coronary artery disease. The results suggest that MIF gene interference is able to inhibit atherosclerotic lesions and increase plaque stability in diabetic apoE−/−mice. MIF inhibition could be a novel and promising approach to the treatment of DM-associated AS.

【 授权许可】

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© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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