title: Collagen type 1 retards tube formation by human microvascular endothelial cells in a fibrin matrix.
abstract: Angiogenesis, or the formation of new microvessels, is often encountered in pathological situations. A fibrinous exudate can often act as a temporary matrix for the ingrowth of these new microvessels. This matrix consists mainly of fibrin, but is mingled with other plasma components and interstitial collagen fibres. In vitro, capillary-like tube formation can be mimicked by exposing human microvascular endothelial cells (hMVECs), seeded on top of a three-dimensional fibrin matrix, to an angiogenic growth factor (e.g. fibroblast growth factor (FGF)-2) and the cytokine tumour necrosis factor (TNF)-alpha. Plasmin activity is required in this process. We investigated whether the angiogenic potential of hMVECs was altered by the presence of collagen. The addition of type I collagen to fibrin matrices dose-dependently inhibited tube-formation. Tube-formation in these fibrin/collagen matrices by hMVECs required matrix metalloprotease (MMP) activity, as well as plasmin activity. On a pure collagen type I matrix, hMVECs were not able to form tube-like structures in the matrix but formed sprouts. This sprouting required MMP activity and was, in contrast to the tube-like structures in a fibrin matrix, not influenced by hypoxia. These data indicate that the interaction between endothelial cells and different matrix components is of importance for the angiogenic potential of these cells.
authors.affiliation: Gaubius Laboratory TNO-PG, Leiden, The Netherlands.
authors.forename: Marielle E
authors.initials: ME
authors.lastname: Kroon
authors.forename: Marianke L J
authors.initials: ML
authors.lastname: van Schie
authors.forename: Bea
authors.initials: B
authors.lastname: van der Vecht
authors.forename: Victor W M
authors.initials: VW
authors.lastname: van Hinsbergh
authors.forename: Pieter
authors.initials: P
authors.lastname: Koolwijk
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods; D024042:Collagen Type I / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008833:Microcirculation / Q000166:cytology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D005337:Fibrin; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases