Endothelial cell injury is involved in atherosclerosis and lupus symptoms in gld.apoE−/− mice
Endothelial cell injury is involved in atherosclerosis and lupus symptoms in gld.apoE−/− mice
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内皮细胞损伤与 gld.apoE 小鼠的动脉粥样硬化和狼疮症状有关
DOI：
10.1111/1756-185x.13458
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发表时间：
2018
影响因子：
2.5
通讯作者：
Lingyun Sun
中科院分区：
文献类型：
--
作者：
Genhong Yao;Jingjing Qi;Zhuoya Zhang;Saisai Huang;Linyu Geng;Wenchao Li;Weiwei Chen;Xiaojun Tang;Shiying Wang;Lingyun Sun
动脉粥样硬化相关的心血管并发症是系统性红斑狼疮（SLE）患者发病和死亡的主要原因。然而，其潜在机制尚未完全了解。内皮功能障碍已被确定为参与心血管疾病和SLE的发病机制。本研究旨在评估狼疮和动脉粥样硬化的组合在小鼠中的内皮细胞损伤。MethodsThe小鼠模型的加速动脉粥样硬化狼疮（gld.apoE−/−小鼠）产生载脂蛋白E-缺陷（apoE−/−）和FaslgldC 57 BL/6小鼠。评价狼疮样自身免疫和动脉粥样硬化病变。结果：建立了双巨噬细胞apoE−/−小鼠模型。与野生型小鼠（WT小鼠）相比，5月龄apoE−/−小鼠的脾脏显著增大。gld.apoE−/−小鼠产生高水平的总免疫球蛋白G（IgG）和IgM，并显示肾小球中IgG和C3沉积显著增加。apoE−/−小鼠表现出典型的SLE肾小球肾炎模式。apoE−/−小鼠的血清肌酐水平较高。在双突变小鼠中，总胆固醇、低密度脂蛋白胆固醇和甘油三酯显著升高，而高密度脂蛋白胆固醇降低。循环内皮祖细胞显著减少。apoE−/−小鼠的血栓调节蛋白和血管细胞粘附分子-1的血清水平显著升高。结论内皮细胞损伤可能是评价SLE心血管疾病风险的生物标志物，靶向内皮细胞功能障碍可能防治SLE动脉粥样硬化。
AimCardiovascular complications related to atherosclerosis are major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). However, the underlying mechanisms are not fully understood. Endothelial dysfunction has been identified as having involvement in pathogenesis of cardiovascular diseases and SLE. This study aims to evaluate endothelial cell injury in mice with the combination of lupus and atherosclerosis.MethodsThe mouse model of accelerated atherosclerosis in lupus (gld.apoE−/−mouse) was generated from apolipoprotein E‐deficient (apoE−/−) and FaslgldC57BL/6 mice. The lupus‐like autoimmunity and atherosclerotic lesions were evaluated. The endothelial cell injury was determined.ResultsThe results showed that the double‐mutantgld.apoE−/−mice were generated. Spleens from 5‐month‐oldgld.apoE−/−mice were significantly enlarged compared with wild‐type mice (WT mice). Thegld.apoE−/−mice produced high levels of total immunoglobulin G (IgG) and IgM and showed marked increase of IgG and C3 deposits in the glomeruli. Thegld.apoE−/−mice displayed a pattern of glomerulonephritis typically found in SLE. Thegld.apoE−/−mice have high levels of serum creatinine. The total cholesterol, low‐density lipoprotein cholesterol and triglycerides were significantly increased, while high‐density lipoprotein cholesterol decreased in the double‐mutant mice. The circulating endothelial progenitor cells were significantly decreased. The serum levels of thrombomodulin and vascular cell adhesion molecule‐1 were significantly elevated ingld.apoE−/−mice. Thegld.apoE−/−mice simultaneously exhibited SLE and atherosclerosis characteristics.ConclusionOur findings indicated that endothelial cell injury might be a biomarker for evaluating risks of cardiovascular disease in SLE and targeting endothelial cell dysfunction might prevent and treat atherosclerosis in SLE.