The Acute Phase Reactant Orosomucoid-1 Is a Bimodal Regulator of Angiogenesis with Time- and Context-Dependent Inhibitory and Stimulatory Properties
Figure 8
Schematic drawing showing regulation of injury-induced angiogenesis by ORM1.
Macrophages produce TNFα in response to injury. TNFα stimulates angiogenesis directly by activating endothelial cells and indirectly by inducing production of VEGF by mural cells. TNFα also induces production of ORM1 by mural cells. ORM1 in turn suppresses TNFα signaling in macrophages and endothelial cells but has no inhibitory effect on mural cell signaling. ORM1 induces VEGF production by macrophages and promotes VEGF-mediated angiogenesis over time. Thus ORM1 fine tunes the angiogenic response by dampening TNFα stimulatory signals and by promoting VEGF-mediated downstream pro-angiogenic effects.