Journal article
Thrombospondin 1 requires von Willebrand factor to modulate arterial thrombosis in mice
Blood, Vol.125(2), pp.399-406
01/08/2015
DOI: 10.1182/blood-2014-06-581942
PMCID: PMC4314536
PMID: 25343959
Abstract
Thrombospondin 1 (TSP1) has been suggested as a counter receptor to platelet glycoprotein Ibα that supports initial platelet adhesion in absence of von Willebrand factor (VWF). Conversely, several other studies have shown that TSP1 interacts with VWF and may play a mechanistic role in modulating thrombosis. However, the in vivo evidence to support this mechanism remains unclear. Using intravital microscopy, in a 10% FeCl3-induced thrombosis model, we report similar platelet adhesion in Tsp1(-/-)/Vwf(-/-) mice compared with littermate Vwf(-/-) mice, suggesting that TSP1 does not mediate initial platelet adhesion in the absence of VWF. Tsp1(-/-) mice exhibited prolonged occlusion time and a significant decrease in the rate of thrombus growth (P < .05 vs wild-type), but not in the initial platelet adhesion. Complete deficiency of VWF abrogated the rate of thrombus growth in Tsp1(-/-) mice; therefore, we generated Tsp1(-/-)/Vwf(+/-) mice to determine whether TSP1 modulates thrombus growth under conditions of partial VWF deficiency. Tsp1(-/-)/Vwf(+/-) mice exhibited delayed thrombus growth kinetics and prolonged occlusion time (P < .05 vs Vwf(+/-)). Finally, we demonstrate that platelet-derived TSP1 modulates arterial thrombosis in vivo. We conclude that TSP1 released from platelets plays a mechanistic role in modulating thrombosis in the presence of VWF.
Details
- Title: Subtitle
- Thrombospondin 1 requires von Willebrand factor to modulate arterial thrombosis in mice
- Creators
- Prem Prakash - Department of Internal Medicine, University of Iowa, Iowa City, IAParesh P Kulkarni - Department of Internal Medicine, University of Iowa, Iowa City, IAAnil K Chauhan - Department of Internal Medicine, University of Iowa, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.125(2), pp.399-406
- DOI
- 10.1182/blood-2014-06-581942
- PMID
- 25343959
- PMCID
- PMC4314536
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Grant note
- R01 HL118246 / NHLBI NIH HHS R01 HL118742 / NHLBI NIH HHS
- Language
- English
- Date published
- 01/08/2015
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094573602771
Metrics
10 Record Views