Premium
Deletion of Rap1 Increases Atherosclerosis Development in ApoE −/− Mice by Increasing Macrophage Infiltration and Foam Cell Formation
Author(s) -
Chen Xinyi,
Xu Aimin,
Tang Eva Hoi Ching
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.568.4
Subject(s) - rap1 , apolipoprotein e , scavenger receptor , foam cell , lipoprotein , chemokine , macrophage , cholesterol , chemistry , inflammation , biology , endocrinology , medicine , microbiology and biotechnology , immunology , signal transduction , biochemistry , disease , in vitro
The telomere‐binding protein, repressor activator protein 1 (Rap1) was recently found to exert many unexpected physiological functions. The present study aimed to investigate whether deletion of Rap1 modulates macrophage behaviors and affects the development of atherosclerosis in mice. Genetic deletion of Rap1 significantly increased the migration ability of macrophages as illustrated by enhanced chemotactic responses towards monocyte chemoattractant protein 1 (CCL2) and macrophage inflammatory protein‐3‐beta (CCL19). Deletion of Rap1 significantly enhanced cholesterol uptake from modified lipoproteins in macrophages and its transformation into foam cells by increasing the expression of scavenger receptor A. To study the effect of Rap1 deletion on atherosclerotic plaque development, Rap1 −/− /ApoE −/− double knockout mice were generated and fed a western diet for 10 weeks. Though total plasma cholesterol, triglycerides and LDL cholesterols were not altered, both the plaque size at aortic root and aortic arch were significantly increased in Rap1 −/− /ApoE −/− mice as compared to Rap1 +/+ ApoE −/− mice. The plaques of Rap1 −/− /ApoE −/− aggregated greater amount of lipid deposits, as indicated by enhanced Oil red O staining within the lesions. Macrophage content was significantly increased in plaques of Rap1 −/− ApoE −/− mice as compared to Rap1 +/+ ApoE −/− controls, while collagen content and vascular smooth muscle cells were decreased. Taken as a whole, deletion of Rap1 promotes plaque growth and decreased plaque stability in ApoE −/− mice. In summary, deletion of Rap1 regulates macrophages behaviors, including promotion of its migratory ability and transformability to foam cells and thereby exacerbates the development of atherosclerosis in mice. Support or Funding Information This work is supported by RGC General Research Fund (Project code: 17157816), The University of Hong Kong This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .