Yao Genhong, Qi Jingjing, Zhang Zhuoya, Huang Saisai, Geng Linyu, Li Wenchao, Chen Weiwei, Tang Xiaojun, Wang Shiying, Sun Lingyun
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Int J Rheum Dis. 2019 Mar;22(3):488-496. doi: 10.1111/1756-185X.13458. Epub 2018 Dec 21.
Cardiovascular 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.
The mouse model of accelerated atherosclerosis in lupus (gld.apoE mouse) was generated from apolipoprotein E-deficient (apoE ) and Fasl C57BL/6 mice. The lupus-like autoimmunity and atherosclerotic lesions were evaluated. The endothelial cell injury was determined.
The results showed that the double-mutant gld.apoE mice were generated. Spleens from 5-month-old gld.apoE mice were significantly enlarged compared with wild-type mice (WT mice). The gld.apoE mice produced high levels of total immunoglobulin G (IgG) and IgM and showed marked increase of IgG and C3 deposits in the glomeruli. The gld.apoE mice displayed a pattern of glomerulonephritis typically found in SLE. The gld.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 in gld.apoE mice. The gld.apoE mice simultaneously exhibited SLE and atherosclerosis characteristics.
Our 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.
与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明确。内皮功能障碍已被证实参与心血管疾病和SLE的发病机制。本研究旨在评估狼疮合并动脉粥样硬化小鼠的内皮细胞损伤情况。
从载脂蛋白E缺陷（apoE⁻/⁻）和Fasl C57BL/6小鼠培育出狼疮加速动脉粥样硬化小鼠模型（gld.apoE⁻/⁻小鼠）。评估狼疮样自身免疫和动脉粥样硬化病变情况。测定内皮细胞损伤情况。
结果显示成功培育出双突变gld.apoE⁻/⁻小鼠。与野生型小鼠（WT小鼠）相比，5月龄gld.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，且肾小球中IgG和C3沉积显著增加。gld.apoE⁻/⁻小鼠呈现出SLE中典型的肾小球肾炎模式。gld.apoE⁻/⁻小鼠的血清肌酐水平较高。双突变小鼠的总胆固醇、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。gld.apoE⁻/⁻小鼠血清中血栓调节蛋白和血管细胞黏附分子-1水平显著升高。gld.apoE⁻/⁻小鼠同时表现出SLE和动脉粥样硬化特征。
我们的研究结果表明，内皮细胞损伤可能是评估SLE患者心血管疾病风险的生物标志物，针对内皮细胞功能障碍可能预防和治疗SLE中的动脉粥样硬化。
