The Acute Phase Reactant Orosomucoid-1 Is a Bimodal Regulator of Angiogenesis with Time- and Context-Dependent Inhibitory and Stimulatory Properties
Figure 6
Effect of ORM1 on signal transduction in aortic explants and isolated endothelial cells, macrophages or mural cells.
(A). ORM1 inhibits injury- and TNFα (20 ng/ml)-induced phosphorylation of MEK1/2 and p38, but has no effect on TNFα -induced phosphorylation of NFκB. (B–C) Injury-induced (B) and TNFα-induced (C) aortic angiogenesis are suppressed by the MEK1/2 inhibitor PD98059 (N = 4; *** = p<0.001) whereas inhibitors of other signaling pathways have no effect or are minimally inhibitory (* = p<0.05). (D). ORM1 inhibits TNFα-induced phosphorylation of MEK1/2 and p38, but has no inhibitory effect on TNFα -induced phosphorylation of NFκB in endothelial cells and macrophages; ORM1 has no effect on TNFα signaling in mural cells. (E). ORM1 has no inhibitory effect on VEGF (10 ng/ml) signaling in endothelial cells. (F). ORM1 dose dependently induces phosphorylation of NFκB in endothelial cells and macrophages, but has no significant effect on MEK1/2 and p38 phosphorylation.