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Oncostatin M induces angiogenesis in vitro and in vivo
M Vasse1, J Pourtau, V Trochon
1Laboratoire DIFEMA, UFR de Médecine et Pharmacie de Rouen, Paris, France.
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.
Insights
Oncostatin M (OSM) significantly promotes angiogenesis in capillary endothelial cells, surpassing VEGF and bFGF in vitro. This suggests OSM
Area of Science:
- Cardiovascular Biology
- Cellular Angiogenesis
- Molecular Medicine
Background:
- Neovascularization of atherosclerotic plaques weakens them, leading to vascular disease complications.
- Macrophages release growth factors that influence angiogenesis.
- Oncostatin M (OSM) role in atherosclerosis development warrants investigation.
Purpose of the Study:
- To analyze the effect of Oncostatin M (OSM) on angiogenesis.
- To compare OSM's angiogenic potential with leukemia inhibitory factor (LIF) and interleukin-6 (IL-6).
- To explore OSM's involvement in atherosclerosis and tumor growth.
Main Methods:
- Assessed endothelial cell proliferation, chemoattraction, and tube formation in vitro (HMEC-1s).
- Evaluated neovascularization in a rabbit corneal model in vivo.
- Investigated OSM's impact on urokinase receptor, VEGF, IL-8, and bFGF levels.
Main Results:
- OSM significantly increased human dermal microvasculature endothelial cell (HMEC-1) proliferation, chemoattraction, and tube formation in vitro.
- In vivo, OSM demonstrated potent neovascularization in a rabbit corneal model, exceeding LIF's effect.
- OSM's proliferative effect on HMEC-1s was linked to increased VEGF secretion but not IL-8 or bFGF.
Conclusions:
- OSM exhibits a potent angiogenic effect on capillary endothelial cells.
- This angiogenic activity suggests OSM's potential role in pathological processes like atherosclerosis and tumor growth.
- OSM's effects are dependent on endothelial cell origin and species.