Cultured endothelial cells from human arteriovenous malformations have defective growth regulation.
Vascular malformations are frequent in newborns, and they persist throughout life, which differentiates them from vascular tumors (eg, hemangiomas). Arteriovenous malformations are high-flow vascular malformations. They are considered nonmalignant but can expand and become a significant clinical risk when extensive. To characterize endothelial cells from arteriovenous malformations (AMEC), we cultured cells obtained from surgical specimens and studied their properties. After selection, the cells that grew out from explants had phenotypic and antigenic features (platelet endothelial cell adhesion molecule, von Willebrand factor) of human endothelial cells. Their spontaneous proliferation rate was higher (1.8 to 6.4 times) than that of human umbilical vein, arterial, or microvascular endothelial cells. The proliferation rate of AMEC was not sensitive to the inhibitory activity of various cytokines (interleukin-1beta, tumor necrosis factor-alpha, transforming growth factor-beta, Interferon-gamma). In basal conditions, intercellular adhesion molecule (ICAM-1) was detected at a higher level of expression (6- to 10-fold) on AMEC, but these cells failed to express E-selectin or the vascular cell adhesion molecule (VCAM-1) after cytokine stimulation. Expression of c-ets-1 proto-oncogene was shown by in situ hybridization. The low response to cytokines, the higher propensity to proliferate, and the ets-1 expression suggest that AMEC have a defective regulation of proliferation that may be due to a reduced apoptotic process.
Wautier
M P
MP
Laboratoire de Biologie Vasculaire et Cellulaire, Unité de Formation et de Recherche Lariboisière-St Louis, Paris 7, INTS, Paris, France. wautier@ints.fr
Boval
B
B
Chappey
O
O
Enjolras
O
O
Wernert
N
N
Merland
J J
JJ
Wautier
J L
JL
D000293:Adolescent; D000328:Adult; D001165:Arteriovenous Malformations / Q000473:pathology* / Q000601:surgery; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003470:Culture Media; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000494:pharmacology*; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005347:Fibroblasts; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D009924:Organ Culture Techniques; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014469:Umbilical Arteries; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D014841:von Willebrand Factor / Q000032:analysis
D003470:Culture Media; D017077:Culture Media, Conditioned; D016207:Cytokines; D019040:E-Selectin; D007375:Interleukin-1; C000715470:MAS1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D007371:Interferon-gamma