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Basic science: Experiment research
e0186 Study on the mechanism of inhibitory effect of CTLA-4Ig fusion protein on atherosclerosis in apoe deficient mice
  1. Li Yujie,
  2. Zheng Dongdan,
  3. Chen Jie,
  4. Li Xin,
  5. Xiong Yan,
  6. Liao Xiaoxing
  1. The First Affiliated Hospital Sun Yatsen University, Guangzhou, China

Abstract

Objective To investigate the mechanism of inhibitory effect of CTLA-4Ig fusion protein on atherosclerosis in mice with an apolipoprotein-E gene defect fed on cholesterol diet.

Methods 30 male 10-week-old apoE(-/-) mice were fed on cholesterol diet and divided into CTLA-4Ig treatment group, IgG1 group and PBS group at random, 10 in each. The three groups were given intraperitoneal injection of CTLA-4Ig (10 μg per time), Rat-IgG1 (10 μg per time), (and) PBS (100 μl per time) respectively, twice a week, for 12 weeks. Followed by a 12-week treatment, the whole aorta from the root to crotch of iliac artery was separated after anaesthesia with the intraperitoneal injection of 1% pentobarbital and the whole (total) blood was taken to obtain serum. Subsequently, the area ratio of plaque and lumen, the thickness ratio of endangium and tunica media, the lipid-soaking extent intra-plaque and the content of collagen fibrils and smooth muscle cells intra-plaque were analysed by image-processing soft. The serum concentration of total cholesterol, CRP, sICAM-1, IFN-γ, IL-10, and TGF-β1 were measured.

Results There were typical atherosclerotic plaque in apoE(-/-) mice fed on cholesterol diet after 12 weeks and it was light in the CTLA-4Ig group. There were statistical value of difference in the area ratio of plaque and lumen, the thickness ratio of endangium and tunica media, the lipid-soaking extent intra-plaque, and the content of collagen fibrils in three groups (p all<0.05). It was found that the area ratio of plaque and lumen, the thickness ratio of endangium and tunica media, and the lipid-soaking extent intra-plaque were significant lower and the content of collagen fibrils was higher in the CTLA-4Ig group than those in the IgG1 group and PBS group (p all<0.05), but there was no significant difference in those between the IgG1 group and PBS group (p all>0.05). There were no significant difference in content of smooth muscle cells in three groups (p>0.05). There were no significant difference in serum concentration of total cholesterol in three groups (p>0.05). There were statistical value of difference in the serum concentration of CRP, sICAM-1, IFN-γ, IL-10, and TGF-β1 in all three groups (p all<0.05). It was found that CTLA-4Ig could decrease the serum concentration of CRP, sICAM-1 and IFN-γ and increase IL-10 and TGF-β1, but IgG1 and PBS.

Conclusions CTLA-4Ig fusion protein could inhibit the (del) atherosclerosis progression in apoE(-/-) mice fed on cholesterol diet and it's effect might be associated with blocking B7/CD28, anti-inflammation, promoting Th2 polarisation and affecting regulate T cells.

  • Atherosclerosis
  • B7/CD28
  • CTLA-4
  • CTLA-4Ig
  • apoE deficient mice
  • mechanism

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