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Tissue factor promotes and stabilizes the vascular phenotype of newly form capillaries
Abstract number: AS-WE-055
Arderiu1 G., Peña1 E., Badimon1 L.
11Cardiovascular Research Center, CSIC-ICCC, Hospital Santa Creu i Sant Pau, Instituto Carlos III CIBERobn, Barcelona, Spain
How-to-cite Arderiu G, Peña E, Badimon L. Tissue factor promotes and stabilizes the vascular phenotype of newly form capillaries. Journal of Thrombosis and Haemostasis 2009; Volume 7, Supplement 2: Abstract AS-WE-055
Tissue factor (TF), the main initiator of coagulation, is expressed around blood vessels and its expression is increased by several inflammatory mediators. Elevated levels of TF are involved in the pathogenesis of atherosclerosis by promoting thrombus formation; in addition, TF expression has been closely linked to angiogenesis and malignancy. Since TF is able to initiate cellular signaling mechanisms leading to alteration in patterns of gene expression, it was our objective to investigate whether TF could trigger and stabilize neovessel formation. We have used a three-dimensional co-culture system with human microvascular endothelial (HMEC-1), human vascular smooth muscle cells (HVSMC) and an in vivo model of xenograft implantation in mouse. We observed by confocal microscopy, that direct contact between HMEC-1 and HVSMC promoted branching morphogenesis in 3D BM cultures. VSMC localize around endothelial cells promoting migration (74 ± 7.3 vs. 23 ± 5.4) of endothelial cells. The induction of this mechanism of formation of complex tube-like structures was inhibited by the inhibition of TF expression (siRNA). Low levels of TF (75% ± 6.5 inhibition vs control) in HMEC-1 resulted in reduced cellular migration as well as upregulation of HAND2 (three folds up), and downregulation of CCL2 (four folds down). Importantly, inhibition of TF expression in either HMEC-1 or HVSMC decreases their shared ability to form new capillaries in mouse xenografts (210.56 ± 15.70 pixels main tub HMEC-1, 263.32 ± 20.45 pixels main tub HVSMC vs. 368.33 ± 15 pixels control), and also increases the permeability of these structures. In conclusion, these results demonstrate that: a) HVSMC not only stabilize HMEC-1 but also play an important role in cell-cell contact participating directly in the formation of capillary-like networks; and, b) TF has a key role in coordinating the formation of neovessels with a stable vascular phenotype.
Disclosure of interest: none declared.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
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