Neovascularization of the atherosclerotic plaque is responsible for its wea
kening and consequently for the complications of vascular disease. Macropha
ges 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 (LLF) and interleukin
-6 (IL-6). On human dermal microvasculature endothelial cells (HMEC-1s), OS
M (22.5 to 112.5 pmol/L) induced a dose-dependent increase in cell prolifer
ation greater than that induced by the classic angiogenic factors vascular
endothelial growth factor (VEGF; 543 pmol/L:) and basic fibroblast growth f
actor (bFGF; 1.1 nmol/L). LIF (19 to 475 pmol/L) induced only a 30% increas
e 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 l
ength, which were already noticeable by day 3. LLF and IL-6 induced a weake
r 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 th
an LIF, the length of the neovessels being longer with OSM than with LIF, w
hereas 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 incr
ease in the urokinase receptor and a 60% increase in VEGF secretion, wherea
s 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 pm
ol/L) did not induce human umbilical vein endothelial cell proliferation an
d even had a small inhibitory effect (17%) on calf pulmonary artery endothe
lial cells. In conclusion, OSM induces an angiogenic effect on capillary en
dothelial cells, which could be, at least in part, implicated in pathologic
al processes such as atherosclerosis or tumor growth.