Blood VEGF, but not tissue VEGF concentration, is dependent on VEGF clearance and vascular permeability. The diseased compartment is not included here. A, Tissue and blood VEGF concentrations increase with VEGF secretion rate. The profile is approximately linear in each case. In the absence of VEGF clearance from the blood, the steady-state free VEGF concentration is the same in the tissue and in the blood (purple line). With a clearance rate of c
= 0.0206 min-1, the blood concentration (red line) is lower than that of the normal tissue (blue dots), which is unchanged by the clearance. Increase in tissue-blood permeability from k
= 4 × 10-8 cm/s (dotted line) to 4 × 10-7 cm/s (dashed line), raises the blood VEGF concentration but not the tissue concentration. B, Increasing transcapillary permeability increases the blood VEGF concentration at steady state. VEGF165 secretion rate q = 0.102 molecule/cell/s, clearance rate c
= 0.0206 min-1 . C, Increased clearance rate of VEGF from the blood decreases blood concentration of VEGF, without decreasing tissue VEGF. VEGF165 secretion rate q = 0.102 molecule/cell/s, vascular permeabilities k
= 4 × 10-8 cm/s (dotted line) and 4 × 10-7 cm/s (dashed line). For all simulations, VEGFR1 = 10,000, VEGFR2 = 10,000 and NRP1 = 10,000 molecules/endothelial cell.