Endothelial cell injury is involved in atherosclerosis and lupus symptoms in gld.apoE- / - mice

Genhong Yao; Jingjing Qi; Zhuoya Zhang; Saisai Huang; Linyu Geng; Wenchao Li; Weiwei Chen; Xiaojun Tang; Shiying Wang; Lingyun Sun

doi:10.1111/1756-185X.13458

Endothelial cell injury is involved in atherosclerosis and lupus symptoms in gld.apoE^- ^/ ^- mice

Int J Rheum Dis. 2019 Mar;22(3):488-496. doi: 10.1111/1756-185X.13458. Epub 2018 Dec 21.

Authors

Affiliation

¹ Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

PMID: 30575313
DOI: 10.1111/1756-185X.13458

Abstract

Aim: 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.

Methods: The mouse model of accelerated atherosclerosis in lupus (gld.apoE^- ^/ ^- mouse) was generated from apolipoprotein E-deficient (apoE^- ^/ ^- ) and Fasl^gld C57BL/6 mice. The lupus-like autoimmunity and atherosclerotic lesions were evaluated. The endothelial cell injury was determined.

Results: 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.

Conclusion: 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.

Keywords: atherosclerosis; endothelial cell injury; systemic lupus erythematosus.

MeSH terms

Animals
Atherosclerosis / genetics
Atherosclerosis / metabolism
Atherosclerosis / pathology*
Autoantibodies / blood
Creatinine / blood
Disease Models, Animal
Dyslipidemias / genetics
Dyslipidemias / metabolism
Dyslipidemias / pathology
E-Selectin / metabolism
Endothelial Cells / metabolism
Endothelial Cells / pathology*
Fas Ligand Protein / deficiency*
Fas Ligand Protein / genetics
Fatty Liver / genetics
Fatty Liver / metabolism
Fatty Liver / pathology
Genetic Predisposition to Disease
Kidney Glomerulus / metabolism
Kidney Glomerulus / pathology
Lupus Erythematosus, Systemic / genetics
Lupus Erythematosus, Systemic / metabolism
Lupus Erythematosus, Systemic / pathology*
Mice, Inbred C57BL
Mice, Knockout, ApoE*
Phenotype
Plaque, Atherosclerotic
Thrombomodulin / metabolism
Vascular Cell Adhesion Molecule-1 / metabolism

Substances

Autoantibodies
E-Selectin
Fas Ligand Protein
Fasl protein, mouse
THBD protein, mouse
Thrombomodulin
Vascular Cell Adhesion Molecule-1
Creatinine

Grants and funding

81001301; 81471533; 81501347; 81571583/National Natural Science Foundation of China