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Free Cholesterol‐Induced Macrophage Proliferation via Peroxisome–Proliferator Activated Receptor Gamma (PPAR Ƴ ) and Cyclin E Signaling Pathway
Author(s) -
Xu Xiaoyang,
Yuan Xinxu,
Zhang Aolin,
Li Ningjun,
Li Pinlan,
Zhang Fan
Publication year - 2015
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.29.1_supplement.631.5
Subject(s) - cell growth , macrophage , chemistry , cell cycle , cyclin d1 , cyclin , medicine , microbiology and biotechnology , cancer research , cell , endocrinology , biology , biochemistry , in vitro
Our recent studies have demonstrated that the buildup of oxLDL‐derived free cholesterol (FC) in macrophages profoundly contributes to the foam cell formation and coronary artery atherosclerosis in CD38 ‐/‐ mice. The current study was designed to investigate the proliferative role of FC in B6 mouse bone ‐ marrow derived macrophages. With the colorimetric analysis of tetrazolium metabolite formazan, it was found that FC from (µg/ml) 0, 5, 10 and 20 to 40 concentration‐dependently increased the macrophage cell proliferation by folds of control at 1.33 , 1.41 and 1.54 to 2.24 , correspondingly. A similar macrophage cell proliferation upon FC treatment was also observed by flow cytometry cell count. Cell cycle assay with propodium iodide revealed that the increased ratio of cell population at S phrase plus G2/M over that at G0/G1 were well correlated with FC concentration enhancement as 0.28 in control; 0.31, 0.39, 0.44 and 0.48 in different FC groups as above. Both real time PCR and Western blot analyses showed that the expressions of cyclin E and PPAR Ƴ significantly increased in the presence of FC (20 mg/ml). PPAR Ƴ gene silencing or blockade of PPAR Ƴ by GW9662 (20 µg/ml) markedly attenuated the expressions of cyclin E and thereby almost abolished macrophage proliferations induced by FC. These results for the first time reveal that FC acts to promote macrophage proliferation via the activation of PPAR Ƴ and cyclin E signaling pathway. Understanding the role of FC in macrophage proliferation may facilitate the development of a novel therapeutic strategy for the prevention and treatment of atherosclerosis (Supported by NIH R01HL115068).