A computational analysis of in vivo VEGFR activation by multiple co-expressed ligands
(A) Predicted free and sR1-bound ligands, and free and ligand-bound sR1 in plasma. (B) Predicted VEGF, PlGF, and sR1 distribution in healthy tissue in “Main Body Mass” compartment, shown in pM of tissue. (C) Extracellular (not bound to or inside ECs) VEGF, PlGF, and sR1 in “Main Body Mass” compartment, in pM of tissue. (D) Steady-state net flow profiles for VEGF, PlGF, sR1, and sR1-ligand complexes between the calf muscle, blood, and main body mass. All VEGF isoforms are aggregated, as are both PlGF isoforms. Green arrows represent production, red arrows EC consumption, black arrows bi-directional vascular permeability, gray arrows lymphatic drainage, and pink arrows with red outlines direct clearance from blood. The white arrows show the net association or dissociation of VEGF-sR1 and PlGF-sR1 complexes in each compartment. Displayed concentrations are free ligand, sR1, or complex in interstitial fluid or plasma. The numbers under each compartment are the respective compartment volumes. Flows are given in pmoles/day. (E) Comparison of VEGF and PlGF isoform distribution with relative isoform production rates demonstrates locations and complexes where each isoform is under- or over-represented relative to the fraction of total VEGF or PlGF production. (F) Matrix site occupancy in the EBM, ECM, and PBM.