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Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13

(2006) BLOOD. 107(3). p.955-964
Author
Organization
Abstract
The function of thrombospondin-1 (TSP-1) in hemostasis was investigated in wild-type (WT) and Tsp1(-/-) mice, via dynamic platelet interaction studies with A23187-stimulated mesenteric endothelium and with photochemically injured cecum subendothelium. Injected calcein-labeled WT platelets tethered or firmly adhered to almost all A23187-stimulated blood vessels of WT mice, but Tsp1(-/-) platelets tethered to 45% and adhered to 25.8% of stimulated Tsp1(-/-) vessels only. Stimulation generated temporary endothelium-associated ultralarge von Willebrand factor (VWF) multimers, triggering platelet string formation in 48% of WT versus 20% of Tsp1(-/-) vessels. Injection of human TSP-1 or thromboticthrombocytopenic purpura (TTP) patient-derived neutralizing anti-ADAMTS13 antibodies corrected the defective platelet recruitment in Tsp1(-/-) mice, while having a moderate effect in WT mice. Photochemical injury of intestinal blood vessels induced thrombotic occlusions with longer occlusion times in Tsp1(-/-) venules (1027 +/- 377 seconds) and arterioles (858 +/- 289 seconds) than in WT vessels (559 +/- 241 seconds, P < .001; 443 +/- 413 seconds, P < .003) due to defective thrombus adherence, resulting in embolization of complete thrombi, a defect restored by both human TSP-1 and antiADAMTS13 antibodies. We conclude that in a shear field, soluble or local platelet-released TSP-1 can protect unfolded endothelium-bound and subendothelial VWF from degradation by plasma ADAMTS13, thus securing platelet tethering and thrombus adherence to inflamed and injured endothelium, respectively.
Keywords
VON-WILLEBRAND-FACTOR, INTEGRIN-ASSOCIATED PROTEIN, THROMBASTHENIC PLATELETS, ACTIVATED PLATELETS, MONOCLONAL-ANTIBODY, ENDOTHELIAL-CELLS, AGGREGATION, RECEPTOR, BINDING, ANGIOGENESIS

Citation

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MLA
Bonnefoy, A, K Daenens, Hendrik Feys, et al. “Thrombospondin-1 Controls Vascular Platelet Recruitment and Thrombus Adherence in Mice by Protecting (sub)endothelial VWF from Cleavage by ADAMTS13.” BLOOD 107.3 (2006): 955–964. Print.
APA
Bonnefoy, A., Daenens, K., Feys, H., De Vos, R., Vandervoort, P., Vermylen, J., Lawler, J., et al. (2006). Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13. BLOOD, 107(3), 955–964.
Chicago author-date
Bonnefoy, A, K Daenens, Hendrik Feys, R De Vos, P Vandervoort, J Vermylen, J Lawler, and MF Hoylaerts. 2006. “Thrombospondin-1 Controls Vascular Platelet Recruitment and Thrombus Adherence in Mice by Protecting (sub)endothelial VWF from Cleavage by ADAMTS13.” Blood 107 (3): 955–964.
Chicago author-date (all authors)
Bonnefoy, A, K Daenens, Hendrik Feys, R De Vos, P Vandervoort, J Vermylen, J Lawler, and MF Hoylaerts. 2006. “Thrombospondin-1 Controls Vascular Platelet Recruitment and Thrombus Adherence in Mice by Protecting (sub)endothelial VWF from Cleavage by ADAMTS13.” Blood 107 (3): 955–964.
Vancouver
1.
Bonnefoy A, Daenens K, Feys H, De Vos R, Vandervoort P, Vermylen J, et al. Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13. BLOOD. 2006;107(3):955–64.
IEEE
[1]
A. Bonnefoy et al., “Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13,” BLOOD, vol. 107, no. 3, pp. 955–964, 2006.
@article{8549123,
  abstract     = {The function of thrombospondin-1 (TSP-1) in hemostasis was investigated in wild-type (WT) and Tsp1(-/-) mice, via dynamic platelet interaction studies with A23187-stimulated mesenteric endothelium and with photochemically injured cecum subendothelium. Injected calcein-labeled WT platelets tethered or firmly adhered to almost all A23187-stimulated blood vessels of WT mice, but Tsp1(-/-) platelets tethered to 45% and adhered to 25.8% of stimulated Tsp1(-/-) vessels only. Stimulation generated temporary endothelium-associated ultralarge von Willebrand factor (VWF) multimers, triggering platelet string formation in 48% of WT versus 20% of Tsp1(-/-) vessels. Injection of human TSP-1 or thromboticthrombocytopenic purpura (TTP) patient-derived neutralizing anti-ADAMTS13 antibodies corrected the defective platelet recruitment in Tsp1(-/-) mice, while having a moderate effect in WT mice. Photochemical injury of intestinal blood vessels induced thrombotic occlusions with longer occlusion times in Tsp1(-/-) venules (1027 +/- 377 seconds) and arterioles (858 +/- 289 seconds) than in WT vessels (559 +/- 241 seconds, P < .001; 443 +/- 413 seconds, P < .003) due to defective thrombus adherence, resulting in embolization of complete thrombi, a defect restored by both human TSP-1 and antiADAMTS13 antibodies. We conclude that in a shear field, soluble or local platelet-released TSP-1 can protect unfolded endothelium-bound and subendothelial VWF from degradation by plasma ADAMTS13, thus securing platelet tethering and thrombus adherence to inflamed and injured endothelium, respectively.},
  author       = {Bonnefoy, A and Daenens, K and Feys, Hendrik and De Vos, R and Vandervoort, P and Vermylen, J and Lawler, J and Hoylaerts, MF},
  issn         = {0006-4971},
  journal      = {BLOOD},
  keywords     = {VON-WILLEBRAND-FACTOR,INTEGRIN-ASSOCIATED PROTEIN,THROMBASTHENIC PLATELETS,ACTIVATED PLATELETS,MONOCLONAL-ANTIBODY,ENDOTHELIAL-CELLS,AGGREGATION,RECEPTOR,BINDING,ANGIOGENESIS},
  language     = {eng},
  number       = {3},
  pages        = {955--964},
  title        = {Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13},
  url          = {http://dx.doi.org/10.1182/blood-2004-12-4856},
  volume       = {107},
  year         = {2006},
}

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