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 fibrin ogen, 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 in duces fibrinogen biosynthesis by hepatocytes and could be implicated i n vascular injury leading to atherosclerosis, we have analyzed the eff ect of oncostatin M on PAI-1, vWf and tPA secretion by endothelial cel ls. A 2-h incubation of human umbilical vein endothelial cells with on costatin M increases thrombin-induced secretion of vWf to the same ext ent as tumour necrosis factor-a or interleukin-1 (137 +/- 26% of contr ol 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 c ells tested. On human umbilical vein endothelial cells, oncostatin M i nduced an increase in PAI-1 and a decrease in tPA secretion, which cou ld explain the thrombogenicity of oncostatin M on large vessels. On a human microvasculature endothelial cell line, oncostatin M did not mod ify PAI-1 but induced an increase in tPA secretion. This observation o f the effects of oncostatin M on both macro- and microvasculature coul d explain the increased levels of vWf, PAI-I and tPA in the plasma of atherosclerotic subjects identified in epidemiological studies, sugges ting that oncostatin M could play a key role in the development of ath erosclerotic lesions. (C) 1998 Lippincott Williams & Wilkins.