Fibrin fragment E stimulates the proliferation, migration and differentiation of human microvascular endothelial cells in vitro.
Various factors involved in haemostasis also regulate the development of new blood vessels by a process called angiogenesis. Enzymatic cleavage of fibrin yields a variety of fibrin degradation products, particularly in areas of intense angiogenesis such as in healing wounds and active atherosclerotic plaques. One of these, fibrin fragment E (FnE), is a potent angiogenic factor in the chick chorioallantoic membrane assay of angiogenesis. Here, we extend these studies to show that FnE stimulates the proliferation, migration and differentiation of human dermal microvascular endothelial cells (HuDMECs) in vitro, both in the absence and presence of such additional endothelial growth factors as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). We also show that these stimulatory effects occur at concentrations of the protein known to be present in angiogenic tissues in vivo. FnE enhanced the angiogenic effects of VEGF or bFGF, indicating a possible synergy between the signalling pathways used by these three angiogenic factors.
Bootle-Wilbraham
C A
CA
Tumour Targeting Group, Section of Pathology, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
Tazzyman
S
S
Thompson
W D
WD
Stirk
C M
CM
Lewis
C E
CE
D000328:Adult; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D016228:Endothelial Growth Factors / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology*; D005338:Fibrin Fibrinogen Degradation Products / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008222:Lymphokines / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D005338:Fibrin Fibrinogen Degradation Products; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C072054:fibrin fragment E-2; D016222:Fibroblast Growth Factor 2