Anti-β(2)GPⅠantibodies accelerate the formation of atherosclerosis in high fat diet fed ApoE deficient mice

Abstract

Objective: To investigate the effects of anti-β(2) glycoprotein Ⅰ(β(2)GPⅠ) antibody on atherosclerosis in ApoE deficient mice. Methods: A total of 24 male ApoE deficient mice of specific pathogen free level(six to eight-week old)were divided into normal control group, high fat diet group, high fat diet with anti-β(2)GPⅠ group, high fat diet with homologous control antibody group (n=6 each group). During the feeding period, mice were weighed every 2 weeks and were intraperitoneally injected with anti-β(2)GPⅠIgG (100 μg/per) and homologous control IgG (100 μg/per) according to grouping once a week. At the 16th week, the carotid arterial lipid deposition was observed by small animal magnetic resonance imaging, and blood samples were collected from internal vein of eyeball and the concentrations of TC, TG, HDL-C and LDL-C in plasma were measured after EDTA anticoagulant treatment. AI was calculated. The mice were then sacrificed and carotid arteries were removed, hematoxylin-eosin staining was used to observe the atherosclerotic lesions near the bifurcation of carotid artery and to calculate lesion size. Results: (1) The body weight of mice was significantly higher in the high fat diet group compared to other 3 groups(all P<0.05), which was similar among high fat diet+ anti-β(2)GPⅠantibody group, high fat diet+ homologous control IgG group and normal diet control group (P>0.05). (2) After 16 weeks, plasma concentrations of TC and LDL-C in high fat diet group, high fat diet+ anti-β(2)GPⅠantibody group and high fat diet+ homologous control IgG group were significantly higher than in normal diet group (all P<0.05), there was no significant difference among high fat diet groups. The level of HDL-C was significantly higher in high fat diet control group than in normal diet control group. The concentration of TG was similar among groups. However, the value of AI in high fat+ anti-β(2)GPⅠ antibody group was significantly higher than in other groups (all P<0.05). (3) After 16 weeks, magnetic resonance imaging revealed that mice in high fat diet+ anti-β(2)GPⅠ antibody group had more obviously lipid deposition in the carotid arteries, it was significantly higher than that in the other groups, and the cross sections of carotid arteries stained with HE also demonstrated obviously carotid lumen stenosis and the percentage of carotid plaque area to carotid artery was (37.545±1.351)% in the high fat diet+ anti-β(2)GPⅠ antibody group, it was significantly higher than normal diet group ((1.235±0.460)%), high fat diet control group((11.635±2.751)%) and high fat diet+ homologous control IgG group ((11.815±2.623)%), all P<0.01. In high fat diet+ anti-β(2)GPⅠ antibody group, the area of carotid plaque was (3.121±0.124)×10(4) μm(2,) it was also significantly higher than normal diet group ((0.094±0.015)×10(4) μm(2)), high fat diet control group ((1.309±0.147)×10(4) μm(2)) and high fat diet+ homologous control IgG group ((1.027±0.228)×10(4)μm(2)), all P<0.01. Conclusion: Anti-β(2)GPⅠ antibody can promote atherosclerotic plaque formation in high fat diet fed ApoE deficient mice.