FIGURE 7.

Angiogenesis regulation by simultaneous modulation of multiple model-identified proteins targets. Shown are the model-predicted (A) VEGF, (B) EC, and (C) collagen concentration time courses during normal angiogenesis (solid black lines), impaired angiogenesis (dashed black lines), and two simulated intervention scenarios wherein multiple proteins and oxygen were simultaneously modulated. In the first intervention, we simulated the simultaneous addition of TGF-β inhibitor at a concentration of 50 nM and decreased the wound oxygen levels to half of normal oxygen levels (dash-dot pink lines). In the second intervention, we simulated the simultaneous addition of TGF-β inhibitor at a concentration of 50 nM along with supplementation of FGF-2 at a concentration of 0.1 ng/mL (dotted pink lines). We simulated impaired angiogenesis by decreasing the VEGF production rate by anti-inflammatory macrophages by 3-fold and increasing the EC apoptosis rate by 1.2-fold. All the interventions were introduced 1 h post-wounding except the reduction in wound oxygen levels which was simulated at day 0 (i.e., at the time of injury).