Thrombogenicity of vascular cells. Comparison between endothelial cells isolated from different sources and smooth muscle cells and fibroblasts.

Zwaginga, Jaap‐Jan; Boer, Hetty C. de; Ijsseldijk, M. J. W.; Kerkhof, A; Müller‐Berghaus, Gert; Gruhlichhenn, J; Sixma, Jan J.; Groot, Philip G. de

doi:10.1161/01.atv.10.3.437

Cited by 52 publications

(41 citation statements)

References 32 publications

(25 reference statements)

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“…Consistent with previous studies, 15,29 fibroblasts and SMCs supported 131-fold and 8.7-fold higher rates of factor Xa generation, respectively, than HUVECs (Table 3). Stimulating HUVECs for 4 hours with 1nM TNF␣ increased factor Xa generation 19.7-fold (Table 3).…”

Section: Fibrin Network Density Correlates With Cellular Expression Osupporting

confidence: 92%

“…As in previous studies, 15,29 thrombin generation on fibroblasts and SMCs demonstrated a significantly shorter lag time, higher rate, shorter time to peak, and increased peak height than on unstimulated HUVECs ( Figure 1A, Table 1). Although the final peak turbidities of all clots were similar, fibroblasts and SMCs supported a significantly faster onset and rate of clot formation than unstimulated HUVECs ( Figure 1B, Table 1).…”

Section: Extravascular Cells Enhance Thrombin Generation and Fibrin Fsupporting

confidence: 84%

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Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability

Campbell

Overmyer

Selzman

et al. 2009

Blood

132

159

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Fibrin is essential for hemostasis; however, abnormal fibrin formation is hypothesized to increase thrombotic risk. We previously showed that in situ thrombin generation on a cell's surface modulates the 3-dimensional structure and stability of the fibrin network. Currently, we compared the abilities of extravascular and intravascular cells to support fibrin formation, structure, and stability. Extravascular cells (fibroblasts, smooth muscle) supported formation of dense fibrin networks that resisted fibrinolysis, whereas unstimulated intravascular (endothelial) cells produced coarse networks that were susceptible to fibrinolysis. All 3 cell types produced a fibrin structural gradient, with a denser network near, versus distal to, the cell surface. Although fibrin structure depended on cellular procoagulant activity, it did not reflect interactions between integrins and fibrin. These findings contrasted with those on platelets, which influenced fibrin structure via interactions between ␤3 integrins and fibrin. Inflammatory cytokines that induced prothrombotic activity on endothelial cells caused the production of abnormally dense fibrin networks that resisted fibrinolysis. Blocking tissue factor activity significantly reduced the density and stability of fibrin networks produced by cytokine-stimulated endothelial cells. Together, these findings indicate fibrin structure and stability reflect the procoagulant phenotype of the endogenous cells, and suggest abnormal fibrin structure is a novel link between inflammation and thrombosis. (Blood. 2009;114:4886-4896)

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Section: Fibrin Network Density Correlates With Cellular Expression Osupporting

confidence: 92%

Section: Extravascular Cells Enhance Thrombin Generation and Fibrin Fsupporting

confidence: 84%

Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability

Campbell

Overmyer

Selzman

et al. 2009

Blood

132

159

View full text Add to dashboard Cite

show abstract

“…Both of these matrices generate considerable amounts of thrombin on their surface when subjected to flowing LMWHanticoagulated blood. 35 The strong inhibition of platelet adhesion to PMAstimulated ECM at high shear rates in comparison with unstimulated ECM or collagen implies not only a more important role for GPIIb/IIIa but also a diminished role for other non-RGD-directed receptors that support platelet adhesion to unstimulated ECM and collagen, like GPIa/IIa 3132 and/or VLA-6. 4 The role of another non-RGD-directed receptor, GPIb, in platelet adhesion to PMA-ECM is not diminished.…”

Section: Adhesion To the Ecmmentioning

confidence: 99%

Aggregate formation is more strongly inhibited at high shear rates by dRGDW, a synthetic RGD-containing peptide.

Saelman¹,

Hese²,

Nieuwenhuis³

et al. 1993

Arterioscler Thromb

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The effect of D-Arg-Gly-Asp-Trp (dRGDW), a synthetic RGD-containing peptide, on platelet adhesion and aggregate formation on various purified adhesive proteins and the extracellular matrix of endothelial cells was investigated with anticoagulated blood recirculating through a parallel-plate perfusion chamber. Aggregate formation on the extracellular matrix of phorbol myristate acetate (PMA)-stimulated endothelial cells and on collagen type I was more strongly inhibited by dRGDW at higher shear rates than at a low shear rate. Platelet adhesion to the extracellular matrix of nonactivated and PMA-stimulated endothelial cells was inhibited by dRGDW, especially at high shear rates, probably as a consequence of the inhibition of platelet spreading. Inhibition by dRGDW of platelet adhesion to von Willebrand factor, fibronectin, and fibrinogen was almost complete, indicating that platelet adhesion to these substrates is mediated through RGD-directed receptors. Platelet adhesion to laminin was not inhibited by the peptide, whereas platelet adhesion to collagen was increased as a consequence of the inhibition of aggregate formation. Our results show that dRGDW is a strong inhibitor of platelet adhesion and aggregate formation, especially at high shear rates. T he interaction of platelets with components present in the vessel wall is a first and essential step in the hemostatic response. A large number of glycoproteins present in the vessel wall, including von Willebrand factor (vWF), fibronectin, various types of collagen (types I, III, and IV), laminin, thrombospondin, and fibrinogen, are involved in adhesion of platelets, their subsequent spreading, and the induction of aggregate formation.

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“…HUVEC are useful in this context because they express low basal levels of tissue factor, a potent coagulation initiator (11). Collagen was selected for the module base material in the prototype because HUVEC naturally reside on a type IV collagen membrane, albeit not the same type as that (type I) which is readily available.…”

mentioning

confidence: 99%

Vascularized organoid engineered by modular assembly enables blood perfusion

McGuigan

Sefton

2006

Proc. Natl. Acad. Sci. U.S.A.

340

299

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Tissue engineering is one approach to address the donor-organ shortage, but to attain clinically significant viable cell densities in thick tissues, laboratory-constructed tissues must have an internal vascular supply. We have adopted a biomimetic approach and assembled microscale modular components, consisting of submillimeter-sized collagen gel rods seeded with endothelial cells (ECs) into a (micro)vascularized tissue; in some prototypes the gel contained HepG2 cells to illustrate the possibilities. The EC-covered modules then were assembled into a larger tube and perfused with medium or whole blood. The interstitial spaces among the modules formed interconnected channels that enabled this perfusion. Viable cell densities were high, within an order of magnitude of cell densities within tissues, and the percolating nature of the flow through the construct was evident in microcomputed tomography and Doppler ultrasound measurements. Most importantly, the ECs retained their nonthrombogenic phenotype and delayed clotting times and inhibited the loss of platelets associated with perfusion of whole blood through the construct. Unlike the conventional scaffold and cell-seeding paradigm of other tissue-engineering approaches, this modular construct has the potential to be scalable, uniform, and perfusable with whole blood, circumventing the limitations of other approaches.collagen gel modules ͉ endothelial cells ͉ tissue engineering

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Thrombogenicity of vascular cells. Comparison between endothelial cells isolated from different sources and smooth muscle cells and fibroblasts.

Cited by 52 publications

References 32 publications

Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability

Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability

Aggregate formation is more strongly inhibited at high shear rates by dRGDW, a synthetic RGD-containing peptide.

Vascularized organoid engineered by modular assembly enables blood perfusion

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