Oncostatin M induces procoagulant activity in human vascular smooth muscle cells by modulating the balance between tissue factor and tissue factor pathway inhibitor.
Oncostatin M (OSM) is a cytokine of the interleukin-6 (IL-6) family secreted by activated monocytes, and is expressed in atherosclerotic plaque. Smooth muscle cells (SMC), by expressing tissue factor (TF) and tissue factor pathway inhibitor (TFPI) can contribute to the thrombogenicity of atherosclerotic plaque. Consequently, the aim of this study was to evaluate the effects of OSM on the procoagulant activity of SMC. We observed that OSM induced in a concentration-dependent manner a potent procoagulant activity (PCA) that was related in part to an increased synthesis of TF, both at the cell membrane and in SMC lysates. The increased expression of TF on SMC membrane induced by OSM was sustained and was still observed 24 h after stimulation by OSM. IL-6 and leukaemia inhibitory factor (LIF), two OSM-related cytokines, did not significantly modify TF expression at the surface of SMC. In addition to its effects on TF, OSM decreased the secretion of TFPI in the supernatants of SMC, as well as in the lysates, but was devoid of effect on TFPI bound at the membrane of SMC. IL-6 and LIF reduced also TFPI secretion, which could explain why the PCA of SMC lysates treated by IL-6 or LIF was increased, despite an absence of effect on TF expression. In conclusion, these data support the hypothesis that by increasing the PCA of SMC, OSM might be involved in the thrombotic complications associated with plaque rupture.
Laboratoire DIFEMA, UFR de Médecine et Pharmacie de Rouen, Rouen, France.
F
F
Mirshahi
M
M
Vasse
A
A
Tedgui
H
H
Li
R
R
Merval
E
E
Legrand
J P
JP
Vannier
J
J
Soria
C
C
Soria
D001011:Aorta; D001161:Arteriosclerosis / Q000150:complications; D002474:Cell-Free System; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D008074:Lipoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology* / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012422:Rupture, Spontaneous; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics
D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008074:Lipoproteins; D008222:Lymphokines; D008565:Membrane Proteins; C508351:OSM protein, human; D010455:Peptides; D011994:Recombinant Proteins; C051928:lipoprotein-associated coagulation inhibitor; D053683:Oncostatin M; D013925:Thromboplastin