Title
TAFI and pancreatic carboxypeptidase B modulate in vitro capillary tube formation by human microvascular endothelial cells
Author
TNO Kwaliteit van Leven
Guimarães, A.H.C.
Laurens, N.
Weijers, E.M.
Koolwijk, P.
van Hinsbergh, V.W.M.
Rijken, D.C.
Publication year
2007
Abstract
OBJECTIVE - Besides having a key role in fibrinolysis, the plasminogen system has been implicated in cell migration and angiogenesis. A common mechanism is the binding of plasminogen to carboxy-terminal lysine residues in partially degraded fibrin or on cellular surfaces. Here we examined the involvement of thrombin activatable fibrinolysis inhibitor (TAFI) and pancreatic carboxypeptidase B (CPB) in an in vitro capillary tube formation system, which is largely plasminogen-dependent. METHODS AND RESULTS - Human microvascular endothelial cells (hMVECs) were seeded on a 3D plasma clot matrix and subsequently stimulated with bFGF/tumor necrosis factor (TNF)-alpha. Tube formation was analyzed and fibrin degradation products (FbDP) were determined in the medium. Supplementation of the matrix with additional TAFI or CPB produced a reduction in tube formation. Pretreatment of hMVECs with CPB before seeding resulted in a similar effect. FbDP-levels indicated a concomitant reduction in matrix proteolysis. A TAFIa inhibitor increased tube formation and FbDP release into the medium. In separate assays, CPB impaired the migration of hMVECs in a dose-dependent manner, whereas proliferation and adhesion remained unaffected. CONCLUSIONS - Overall, these results demonstrate that TAFI and CPB in these systems modulate the plasminogen system both in the matrix and on the cell surface, thus leading to the inhibition of endothelial cell movement and tube formation. © 2007 American Heart Association, Inc.
Subject
Biomedical Research
Angiogenesis
Carboxypeptidase B
Plasma clot matrix
Plasminogen
TAFI
Angiogenesis Inhibitors
Atherosclerosis
Capillaries
Carboxypeptidase B
Carboxypeptidase U
Cell Adhesion
Cell Culture Techniques
Cell Movement
Cell Proliferation
Cells, Cultured
Dose-Response Relationship, Drug
Endothelial Cells
Fibrin
Fibrin Fibrinogen Degradation Products
Fibroblast Growth Factor 2
Humans
Neovascularization, Physiologic
Plant Proteins
Plasminogen
Protease Inhibitors
Time Factors
Tumor Necrosis Factor-alpha
Urinary Plasminogen Activator
Wound Healing
To reference this document use:
http://resolver.tudelft.nl/uuid:82016b3c-34d1-4287-ad19-08b74c737eca
DOI
https://doi.org/10.1161/atvbaha.107.150144
TNO identifier
240225
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 27 (27), 2157-2162
Document type
article