Platelets express and release osteocalcin and co-localize in human calcified atherosclerotic plaques
Article first published online: 7 FEB 2013
© 2012 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 11, Issue 2, pages 357–365, February 2013
How to Cite
FORESTA, C., STRAPAZZON, G., DE TONI, L., FABRIS, F., GREGO, F., GEROSA, G., VETTORE, S. and GAROLLA, A. (2013), Platelets express and release osteocalcin and co-localize in human calcified atherosclerotic plaques. Journal of Thrombosis and Haemostasis, 11: 357–365. doi: 10.1111/jth.12088
- Issue published online: 7 FEB 2013
- Article first published online: 7 FEB 2013
- Accepted manuscript online: 3 DEC 2012 12:02PM EST
- Received 9 May 2012, accepted 13 November 2012
- vascular calcification
Summary. Background: Although vascular-calcification mechanisms are only partially understood, the role of circulating calcifying cells and non-collagenous bone matrix proteins in the bone–vascular axis is emerging. In spite of the fact that platelets represent a cellular interface between hemostasis, inflammation and atherosclerosis, and have a myeloid precursor, a possible involvement in the modulation of vascular calcification has rarely been investigated. We investigated if osteocalcin (OC) is released by platelets and described OC expression in patients with carotid artery occlusive disease.
Methods: Expression and release of OC were determined by Western blot, immunofluorescence, fluorescence-activated cell sorting (FACS) and ELISA in human resting and activated platelets and megakaryocytes. Co-localization of platelet aggregates, macrophages, OC and calcifications was studied in carotid endarterectomy specimens and normal tissues.
Results: Human platelets expressed OC and co-localized with CD63 in δ-granules. Upon activation with an endogenous mechanism, platelets released OC in the extracellular medium. Expression of OC in megakaryocytes suggested lineage specificity. The OC count in circulating platelets and the released amount were significantly higher in patients with carotid artery occlusive disease than in healthy controls (P < 0.0001) in spite of similar serum levels. In atherosclerotic plaques, OC strongly overlapped with CD41+ platelets in the early stage of calcification, but this was not seen in normal tissues. CD68+OC+ cells were present at the periphery of the calcified zone.
Conclusions: Given the active role played by platelets in the atherosclerotic process, the involvement of OC release from platelets in atherosclerotic lesions and the impact of genetic and cardiovascular risk factors in mediating bone-marrow preconditioning should be investigated further.