title: Serum amyloid A directly accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice.
abstract: Although serum amyloid A (SAA) is an excellent marker for coronary artery disease, its direct effect on atherogenesis in vivo is obscure. In this study we investigated the direct effect of SAA on promoting the formation of atherosclerosis in apolipoprotein E-deficient (ApoE⁻/⁻) mice. Murine SAA lentivirus was constructed and injected into ApoE⁻/⁻ mice intravenously. Then, experimental mice were fed a chow diet (5% fat and no added cholesterol) for 14 wks. The aortic atherosclerotic lesion area was larger with than without SAA treatment. With increased SAA levels, the plasma levels of interleukin-6 and tumor necrosis factor-α were significantly increased. Macrophage infiltration in atherosclerotic regions was enhanced with SAA treatment. A migration assay revealed prominent dose-dependent chemotaxis of SAA to macrophages. Furthermore, the expression of monocyte chemotactic protein-1 and vascular cell adhesion molecule-1 (VCAM-1) was upregulated significantly with SAA treatment. SAA-induced VCAM-1 production was detected in human aortic endothelial cells in vitro. Thus, an increase in plasma SAA directly accelerates the progression of atherosclerosis in ApoE⁻/⁻ mice. SAA is not only a risk marker for atherosclerosis but also an active participant in atherogenesis.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Dong
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.forename: Weidong
authors.initials: W
authors.lastname: Qin
authors.forename: Chuankai
authors.initials: C
authors.lastname: An
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Wang
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Fengshuang
authors.initials: F
authors.lastname: An
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood* / Q000473:pathology*; D001835:Body Weight; D018932:Chemokine CCL2 / Q000378:metabolism; D059305:Diet, High-Fat; D018450:Disease Progression; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D018932:Chemokine CCL2; C489995:Saa2 protein, mouse; D000685:Serum Amyloid A Protein; D019010:Vascular Cell Adhesion Molecule-1