title: Oncostatin M induces angiogenesis in vitro and in vivo.
abstract: Neovascularization of the atherosclerotic plaque is responsible for its weakening and consequently for the complications of vascular disease. Macrophages are a source of growth factors that can modulate angiogenesis. In this study, we analyzed the effect of oncostatin M (OSM) on angiogenesis, as it could be involved in the development of atherosclerosis. The effect of OSM was compared with those of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). On human dermal microvasculature endothelial cells (HMEC-1s), OSM (22.5 to 112.5 pmol/L) induced a dose-dependent increase in cell proliferation greater than that induced by the classic angiogenic factors vascular endothelial growth factor (VEGF; 543 pmol/L) and basic fibroblast growth factor (bFGF; 1.1 nmol/L). LIF (19 to 475 pmol/L) induced only a 30% increase in cell proliferation, and IL-6 had no effect. Furthermore, in a modified Boyden-chamber model, OSM, LIF, and IL-6 were chemoattractant for HMEC-1s. In a tridimensional gel of fibrin, OSM increased tube formation and tube length, which were already noticeable by day 3. LIF and IL-6 induced a weaker effect that was only obvious by day 10. The angiogenic effect of OSM was also demonstrated in vivo in a rabbit corneal model: OSM was more potent than LIF, the length of the neovessels being longer with OSM than with LIF, whereas IL-6 was without effect. We tested factors that could be involved in the proliferative effect of OSM on HMEC-1s. OSM induced only a slight increase in the urokinase receptor and a 60% increase in VEGF secretion, whereas it does not modify IL-8 secretion or bFGF levels. The effect of OSM seems to depend on endothelial cell origin and cell species: OSM (up to 112.5 pmol/L) did not induce human umbilical vein endothelial cell proliferation and even had a small inhibitory effect (17%) on calf pulmonary artery endothelial cells. In conclusion, OSM induces an angiogenic effect on capillary endothelial cells, which could be, at least in part, implicated in pathological processes such as atherosclerosis or tumor growth.
authors.affiliation: Laboratoire DIFEMA, UFR de Médecine et Pharmacie de Rouen, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Vasse
authors.forename: J
authors.initials: J
authors.lastname: Pourtau
authors.forename: V
authors.initials: V
authors.lastname: Trochon
authors.forename: M
authors.initials: M
authors.lastname: Muraine
authors.forename: J P
authors.initials: JP
authors.lastname: Vannier
authors.forename: H
authors.initials: H
authors.lastname: Lu
authors.forename: J
authors.initials: J
authors.lastname: Soria
authors.forename: C
authors.initials: C
authors.lastname: Soria
mesh_terms: D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division; D002630:Chemotactic Factors / Q000502:physiology; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis / Q000494:pharmacology; D008833:Microcirculation / Q000166:cytology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D010960:Plasminogen Activators / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D002630:Chemotactic Factors; D016228:Endothelial Growth Factors; D006131:Growth Inhibitors; D015850:Interleukin-6; D016209:Interleukin-8; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; C508351:OSM protein, human; C524898:PLAUR protein, human; D010455:Peptides; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D053683:Oncostatin M; D010960:Plasminogen Activators