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

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 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.