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Molecular Medicine

, Volume 17, Issue 11–12, pp 1357–1364 | Cite as

Serum Amyloid A Directly Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice

  • Zhe Dong
  • Tingting Wu
  • Weidong Qin
  • Chuankai An
  • Zhihao Wang
  • Mingxiang Zhang
  • Yun Zhang
  • Cheng Zhang
  • Fengshuang An
Research Article

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.

Notes

Acknowledgments

This study was supported by the National 973 Basic Research program (2009CB521904), the grant of Natural Science Foundation of Shandong Province (Y2007C074) and Independent Innovation Foundation of Shandong University (2009DX004).

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Zhe Dong
    • 1
  • Tingting Wu
    • 1
  • Weidong Qin
    • 1
  • Chuankai An
    • 2
  • Zhihao Wang
    • 1
  • Mingxiang Zhang
    • 1
  • Yun Zhang
    • 1
  • Cheng Zhang
    • 1
  • Fengshuang An
    • 1
  1. 1.Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of HealthShandong University Qilu HospitalJinan, ShandongChina
  2. 2.School of Electronics Engineering and Computer SciencePeking UniversityBeijingChina

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