Myeloid calcifying cells promote atherosclerotic calcification via paracrine activity and allograft inflammatory factor-1 overexpression
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  • 作者:Mattia Albiero (1)
    Marcello Rattazzi (2)
    Lisa Menegazzo (1) (2)
    Elisa Boscaro (1)
    Roberta Cappellari (2)
    Elisa Pagnin (2)
    Elisa Bertacco (2)
    Nicol Poncina (1) (2)
    Kenneth Dyar (1)
    Stefano Ciciliot (1) (2)
    Kazuya Iwabuchi (3)
    Renato Millioni (4)
    Giorgio Arrigoni (4) (5)
    Nicolle Kraenkel (6) (7)
    Ulf Landmesser (6) (7)
    Carlo Agostini (1) (2)
    Angelo Avogaro (1) (2)
    Gian Paolo Fadini (1) (2)
  • 关键词:Monocytes ; Plaques ; Smooth muscle cells
  • 刊名:Basic Research in Cardiology
  • 出版年:2013
  • 出版时间:July 2013
  • 年:2013
  • 卷:108
  • 期:4
  • 全文大小:2107KB
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  • 作者单位:Mattia Albiero (1)
    Marcello Rattazzi (2)
    Lisa Menegazzo (1) (2)
    Elisa Boscaro (1)
    Roberta Cappellari (2)
    Elisa Pagnin (2)
    Elisa Bertacco (2)
    Nicol Poncina (1) (2)
    Kenneth Dyar (1)
    Stefano Ciciliot (1) (2)
    Kazuya Iwabuchi (3)
    Renato Millioni (4)
    Giorgio Arrigoni (4) (5)
    Nicolle Kraenkel (6) (7)
    Ulf Landmesser (6) (7)
    Carlo Agostini (1) (2)
    Angelo Avogaro (1) (2)
    Gian Paolo Fadini (1) (2)

    1. Venetian Institute of Molecular Medicine, Padova, Italy
    2. Department of Medicine, University of Padova, Via Giustiniani, 2, 35100, Padova, Italy
    3. Department of Immunology, Kitasato School of Medicine, Tokyo, Japan
    4. Proteomic Center of Padova University, Padova, Italy
    5. Department of Biomedical Sciences, University of Padova, Padova, Italy
    6. Institute of Physiology, Cardiovascular Research, University of Zurich, Zurich, Switzerland
    7. Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
  • ISSN:1435-1803
文摘
Several cell types contribute to atherosclerotic calcification. Myeloid calcifying cells (MCCs) are monocytes expressing osteocalcin (OC) and bone alkaline phosphatase (BAP). Herein, we tested whether MCCs promote atherosclerotic calcification in vivo. We show that the murine spleen contains OC+BAP+ cells with a phenotype similar to human MCCs, a high expression of adhesion molecules and CD11b, and capacity to calcify in vitro and in vivo. Injection of GFP+ OC+BAP+ cells into 8- or 40-week ApoE??/sup> mice led to more extensive calcifications in atherosclerotic areas after 24 or 4?weeks, respectively, compared to control OC?/sup>BAP?/sup> cells. Despite that OC+BAP+ cells had a selective transendothelial migration capacity, tracking of the GFP signal revealed that presence of injected cells within atherosclerotic areas was an extremely rare event and so GFP mRNA was undetectable by qPCR of lesion extracts. By converse, injected OC+BAP+ cells persisted in the bloodstream and bone marrow up to 24?weeks, suggesting a paracrine effect. Indeed, OC+BAP+ cell-conditioned medium (CM) promoted calcification by cultured vascular smooth muscle cells (VSMC) more than CM from OC?/sup>BAP?/sup> cells. A genomic and proteomic investigation of MCCs identified allograft inflammatory factor (AIF)-1 as a potential candidate of this paracrine activity. AIF-1 stimulated VSMC calcification in vitro and monocyte-specific (CD11b-driven) AIF-1 overexpression in ApoE??/sup> mice increased calcium content in atherosclerotic areas. In conclusion, we show that murine OC+BAP+ cells correspond to human MCCs and promote atherosclerotic calcification in ApoE??/sup> mice, through paracrine activity and modulation of resident cells by AIF-1 overexpression.

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