A Compartment Model of VEGF Distribution in Humans in the Presence of Soluble VEGF Receptor-1 Acting as a Ligand Trap
Figure 3
Targeting Control sVEGFR1-Secretion Rates (qsR1) for Basal Profile of Healthy Subject.
A: Steady-state sensitivity of plasma and interstitial concentrations of free VEGF (top row) and free sVEGFR1 (bottom row) to qsR1 from normal tissue (y-axis) and calf (x-axis). Top row: Interstitial free VEGF decreased while plasma free VEGF increased with increasing qsR1. Blue/black arrows indicate inverse/direct relation between VEGF concentrations and sVEGFR1-secretion rates. Bottom Row: The targeted 100 pM of free sVEGFR1 was reached in plasma at the control secretion rates of qsR1,Ctrl = (qsR1,Normal, qsR1,Calf) = (0.0107,0.0210) molecule/EC/s. Beige spheres mark the interstitial and plasma sVEGFR1 levels reached at qsR1,Ctrl. B: Density of VEGF-VEGFR complexes were insensitive to qsR1. Bracketed percentages are VEGF-bound fractional occupancies of total VEGFR, averaged (range<0.4%) between normal and calf compartments. In figure: ‘+’ = control; ‘max’, ‘min’ and ‘mean’ indicate targeted ranges; ‘EC’ = endothelial cell; ‘V121’ = VEGF121; ‘V165’ = VEGF165; ‘R1’ = VEGFR1; ‘sR1’ = sVEGFR1; ‘R2’ = VEGFR2.