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- Title
Myeloid calcifying cells promote atherosclerotic calcification via paracrine activity and allograft inflammatory factor-1 overexpression.
- Authors
Albiero, Mattia; Rattazzi, Marcello; Menegazzo, Lisa; Boscaro, Elisa; Cappellari, Roberta; Pagnin, Elisa; Bertacco, Elisa; Poncina, Nicol; Dyar, Kenneth; Ciciliot, Stefano; Iwabuchi, Kazuya; Millioni, Renato; Arrigoni, Giorgio; Kraenkel, Nicolle; Landmesser, Ulf; Agostini, Carlo; Avogaro, Angelo; Fadini, Gian
- Abstract
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 OCBAP 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 OCBAP cells into 8- or 40-week ApoE mice led to more extensive calcifications in atherosclerotic areas after 24 or 4 weeks, respectively, compared to control OCBAP cells. Despite that OCBAP 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 OCBAP cells persisted in the bloodstream and bone marrow up to 24 weeks, suggesting a paracrine effect. Indeed, OCBAP cell-conditioned medium (CM) promoted calcification by cultured vascular smooth muscle cells (VSMC) more than CM from OCBAP 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 mice increased calcium content in atherosclerotic areas. In conclusion, we show that murine OCBAP cells correspond to human MCCs and promote atherosclerotic calcification in ApoE mice, through paracrine activity and modulation of resident cells by AIF-1 overexpression.
- Subjects
ATHEROSCLEROSIS; PARACRINE mechanisms; HOMOGRAFTS; INFLAMMATION; GENE expression; CALCIFICATION; CELL adhesion molecules
- Publication
Basic Research in Cardiology, 2013, Vol 108, Issue 4, p1
- ISSN
0300-8428
- Publication type
Article
- DOI
10.1007/s00395-013-0368-7