In-vitro effect of oncostatin M on the release by endothelial cells of von Willebrand factor, tissue-type plasminogen activator and plasminogen activator inhibitor-1.
Epidemiological studies have demonstrated that levels of plasma fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) are associated with the incidence of vascular disease. Since oncostatin M dramatically induces fibrinogen biosynthesis by hepatocytes and could be implicated in vascular injury leading to atherosclerosis, we have analyzed the effect of oncostatin M on PAI-1, vWf and tPA secretion by endothelial cells. A 2-h incubation of human umbilical vein endothelial cells with oncostatin M increases thrombin-induced secretion of vWf to the same extent as tumour necrosis factor-alpha or interleukin-1 (137+/-26% of control for 5 ng/ml oncostatin M, P < 0.001, n=5). The effects on tPA and PAI-1 secretion were different depending on the type of endothelial cells tested. On human umbilical vein endothelial cells, oncostatin M induced an increase in PAI-1 and a decrease in tPA secretion, which could explain the thrombogenicity of oncostatin M on large vessels. On a human microvasculature endothelial cell line, oncostatin M did not modify PAI-1 but induced an increase in tPA secretion. This observation of the effects of oncostatin M on both macro- and microvasculature could explain the increased levels of vWf, PAI-1 and tPA in the plasma of atherosclerotic subjects identified in epidemiological studies, suggesting that oncostatin M could play a key role in the development of atherosclerotic lesions.
Pourtau
J
J
DIFEMA, Faculté de Médecine et de Pharmacie de Rouen, Saint Etienne du Rouvray, France.
Soria
C
C
Paysant
J
J
Vannier
J P
JP
Vasse
M
M
D001161:Arteriosclerosis / Q000209:etiology; D001777:Blood Coagulation; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
D006131:Growth Inhibitors; C508351:OSM protein, human; D010455:Peptides; D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D053683:Oncostatin M; D010959:Tissue Plasminogen Activator