Collagen type 1 retards tube formation by human microvascular endothelial cells in a fibrin matrix.
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.
Kroon
Marielle E
ME
Gaubius Laboratory TNO-PG, Leiden, The Netherlands.
van Schie
Marianke L J
ML
van der Vecht
Bea
B
van Hinsbergh
Victor W M
VW
Koolwijk
Pieter
P
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
D024042:Collagen Type I; D005337:Fibrin; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases