Role of fibrin and plasminogen activators in repair-associated angiogenesis: in vitro studies with human endothelial cells.
Angiogenesis, the formation of new blood vessels from existing ones, plays a central role in development and in a number of pathological conditions. Tissue repair-associated angiogenesis usually involves cell invasion into a fibrin structure and the presence of inflammatory cells. In this chapter the role of plasminogen activators in the dissolution of fibrin and the invasion of endothelial cells into a fibrin matrix is described. Tissue-type plasminogen activator is stored in endothelial cells and can be released acutely into the vessel lumen upon stimulation of the endothelium to activate fibrinolysis and to prevent fibrin deposition. At the basolateral side of the cell, urokinase-type plasminogen activator (uPA) bound to a specific cellular receptor is involved in the proteolytic modulation of matrix proteins and cell-matrix interaction. The cytokine tumor necrosis factor-alpha (TNF-alpha) cooperates with the angiogenic factors basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in inducing human microvascular endothelial cells in vitro to invade a three dimensional fibrin matrix and to form capillary-like tubular structures. The formation of these capillary-like tubules requires cell-bound uPA activity.
van Hinsbergh
V W
VW
Gaubius Laboratory TNO-PG, Leiden, The Netherlands.
Koolwijk
P
P
Hanemaaijer
R
R
D000818:Animals; D016228:Endothelial Growth Factors / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005337:Fibrin / Q000502:physiology*; D005342:Fibrinolysis; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D008222:Lymphokines / Q000502:physiology; D008666:Metalloendopeptidases / Q000378:metabolism; D008833:Microcirculation / Q000502:physiology*; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D010960:Plasminogen Activators / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D006133:Growth Substances; D008222:Lymphokines; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D005337:Fibrin; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D008666:Metalloendopeptidases