Imperial College London
Alternate

DrKoraliaPaschalaki

Faculty of Medicine, National Heart & Lung Institute

Senior Clinical Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2728k.paschalaki Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Starke:2013:10.1182/blood-2012-06-435727,
author = {Starke, RD and Paschalaki, KE and Dyer, CE and Harrison-Lavoie, KJ and Cutler, JA and McKinnon, TA and Millar, CM and Cutler, DF and Laffan, MA and Randi, AM},
doi = {10.1182/blood-2012-06-435727},
journal = {Blood},
pages = {2773--2784},
title = {Cellular and molecular basis of von Willebrand disease: studies on blood outgrowth endothelial cells},
url = {http://dx.doi.org/10.1182/blood-2012-06-435727},
volume = {121},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Von Willebrand disease (VWD) is a heterogeneous bleeding disorder caused by decrease or dysfunction of von Willebrand factor (VWF). A wide range of mutations in the VWF gene have been characterized; however, their cellular consequences are still poorly understood. Here we have used a recently developed approach to study the molecular and cellular basis of VWD. We isolated blood outgrowth endothelial cells (BOECs) from peripheral blood of 4 type 1 VWD and 4 type 2 VWD patients and 9 healthy controls. We confirmed the endothelial lineage of BOECs, then measured VWF messenger RNA (mRNA) and protein levels (before and after stimulation) and VWF multimers. Decreased mRNA levels were predictive of plasma VWF levels in type 1 VWD, confirming a defect in VWF synthesis. However, BOECs from this group of patients also showed defects in processing, storage, and/or secretion of VWF. Levels of VWF mRNA and protein were normal in BOECs from 3 type 2 VWD patients, supporting the dysfunctional VWF model. However, 1 type 2M patient showed decreased VWF synthesis and storage, indicating a complex cellular defect. These results demonstrate for the first time that isolation of endothelial cells from VWD patients provides novel insight into cellular mechanisms of the disease
AU  - Starke,RD
AU  - Paschalaki,KE
AU  - Dyer,CE
AU  - Harrison-Lavoie,KJ
AU  - Cutler,JA
AU  - McKinnon,TA
AU  - Millar,CM
AU  - Cutler,DF
AU  - Laffan,MA
AU  - Randi,AM
DO  - 10.1182/blood-2012-06-435727
EP  - 2784
PY  - 2013///
SP  - 2773
TI  - Cellular and molecular basis of von Willebrand disease: studies on blood outgrowth endothelial cells
T2  - Blood
UR  - http://dx.doi.org/10.1182/blood-2012-06-435727
UR  - pm:23355534
VL  - 121
ER  -
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