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AB0130 Premature atherosclerosis of apoe-/-fasl-/- c57bl/6 mice was mediated by dysfunction of bone marrow derived endothelial progenitor cells
  1. L. Sun1,
  2. L. Geng1,
  3. S. Wang1,
  4. D. Wang1,
  5. X. Li1
  1. 1Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

Abstract

Background Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous manifestations including severe organ damage and premature atherosclerosis. A mouse model of apolipoprotein E-deficient (apoE(-/-)) and Fas ligand-deficient (FasL(-/-)) showed accelerated atherosclerosis in lupus. Endothelial progenitor cells (EPCs) are a population of cells able to differentiate into endothelial cells and participating in the formation of blood vessels, its number and function play an important role in the development of atherosclerosis.

Objectives To investigate the number and function of EPCs in Apoe-/-FasL-/- C57BL/6 mice, and to detect whether premature atherosclerosisof Apoe-/-FasL-/- C57BL/6 mice was mediated by dysfunction of these EPCs.

Methods EPCs were isolated from peripherial blood, bone marrow and spleen of four types of C57BL/6 mice, ApoE+/+FasL+/+, ApoE+/+FasL-/-, ApoE-/-FasL+/+, ApoE-/-FasL-/-, growth and morphology changes of cultured and expanded EPCs from Bone marrow were observed under inverted microscope for 2 weeks. The percentage of EPCs was analyzed by FACS as CD11b-Sca-1+CD309+ cells. The attached cells were stained with Dil labeled acetylated low-density lipoprotein (Dil-ac-LDL) and FITC-labeled Ulex europaeus agglutinin 1(FITC-UEA-1) double dyeing to determine their swallow function. The adherent function of EPCs was determined by counting the number of recultured EPCs. The capacity of EPCs to form the cavity structure was detected by counting the number of formed vascular-like structure.

Results The percentage of circulating EPCs was significantly decreased in ApoE-/-FasL-/- group (0.012% ± 0.008%) compared to ApoE+/+FasL+/+(0.034% ± 0.007%, P < 0.01), ApoE+/+FasL-/-(0.021% ± 0.002%, P<0.05), and ApoE-/-FasL+/+ group(0.018%±0.003%, P<0.05). The percentage of bone marrow derived EPCs was decreased in ApoE-/-FasL-/- group (0.12% ± 0.08%) compared to ApoE+/+FasL+/+(0.41% ± 0.11%, P < 0.05), ApoE+/+FasL-/-(0.17% ± 0.02%, P<0.05), and ApoE-/-FasL+/+ group(0.14%±0.03%, P<0.05). The weights of spleen and kidney of ApoE-/-FasL-/- mice were increased, while the percentage of spleen EPCs was significantly decreased (0.012%±0.003%, P<0.05). The percentage of Di-lac-LDL and FITC-UEA-1 double positive cells was decreased in ApoE-/-FasL-/- group (58% ±9%) compared to ApoE+/+FasL+/+(87%±10%, P< 0.05), ApoE+/+FasL-/-(82%±7%, P<0.05), and ApoE-/-FasL+/+ group(67%±7%, P<0.05). The adherent function of EPCs was decreased in ApoE-/-FasL-/- group (44%±8%) compared to ApoE+/+FasL+/+(82%±11%, P<0.01), ApoE+/+FasL-/-(72%±7%, P<0.05), and ApoE-/-FasL+/+ group(68%±3%, P<0.05). The capacity of EPCs to form the cavity structure was decreased in ApoE-/-FasL-/- group (4.0±0.8) compared to ApoE+/+FasL+/+(12.0±1.4, P<0.01), ApoE+/+FasL-/-(8.0±1.0, P<0.05), and ApoE-/-FasL+/+ group(6.5±1.2, P<0.05), respectively.

Conclusions Premature atherosclerosisof Apoe-/-FasL-/- C57BL/6 mice was associated with decreased number and dysfunction of EPCs.

Disclosure of Interest None Declared

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