Bone morphogenetic protein -7 increases thrombogenicity of lipid-rich atherosclerotic plaques via activation of tissue factor

Thrombosis Research
Mikhail A SovershaevJ B Hansen

Abstract

Thrombogenicity of atherosclerotic plaques largely depends on plaque morphology. Tissue factor (TF) expression is higher in lipid-rich than in calcified lesions. Although bone morphogenetic protein (BMP) -7 is a known inhibitor of vascular calcification, the role of BMP-7 in the development of plaque thrombogenicity is uncertain. We hypothesized that increased thrombogenic potential of lipid-rich plaques is attributed to activation of TF by BMP-7. We measured levels of BMP-7 and TF proteins in lipid-rich and calcified carotid plaques, and tested the effects of BMP-7 on TF expression in human monocytes in vitro. Quantitative immunohistochemical analysis of endarterectomy specimens for TF and BMP-7 revealed that lipid-rich plaques contained more TF antigen than calcified ones (158.6±25.3 vs 37.4±8.8 AU, p<0.008). Lipid-rich plaques also expressed higher levels of BMP-7 (60.7±5.2 AU) than calcified lesions (31.8±8.6 AU, p<0.021). In vitro treatment of whole blood with BMP-7 markedly increased the population of TF-positive monocytes from 1.5±0.6 % to 31.0±7.6 % (p<0.001). Stimulation of blood with BMP-7 was accompanied by elevated surface presentation of TF antigen in monocytes as TF-dependent fluorescence intensity increased from ...Continue Reading

References

Jul 1, 1975·British Journal of Haematology·R P RiversW L Weston
Dec 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·N S CunninghamA H Reddi
Apr 1, 1993·The Journal of Clinical Investigation·K BoströmL L Demer
May 1, 1997·The New England Journal of Medicine·A P BurkeR Virmani
Sep 1, 1996·Current Opinion in Hematology·W Ruf, B M Mueller
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·F SamadD J Loskutoff
Apr 25, 2000·The EMBO Journal·J Massagué, D Wotton
Feb 15, 2001·Annals of Internal Medicine·U RauchJ H Chesebro
May 16, 2003·Nature·Shun-ichi Harada, Gideon A Rodan
May 23, 2003·Journal of the American Society of Nephrology : JASN·Matthew R DaviesKeith A Hruska
Jun 13, 2003·Journal of Interventional Cardiology·Renu VirmaniAndrew Farb
Apr 23, 2004·American Journal of Physiology. Endocrinology and Metabolism·Radhika Vattikuti, Dwight A Towler
Feb 10, 2006·Blood Cells, Molecules & Diseases·Nigel Mackman
Nov 30, 2006·Current Opinion in Hematology·Kevin Croce, Peter Libby
Apr 16, 2008·Journal of Internal Medicine·T ThimE Falk
Mar 13, 2010·Journal of the American College of Cardiology·Armin J ReiningerWolfgang Siess

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Citations

Dec 24, 2014·Thrombosis Research·T A SovershaevM A Sovershaev
Sep 8, 2011·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Elena M EgorinaJohn-Bjarne Hansen

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