| Interstitial VEGF in muscle, [V]IS = 10 pM |
[V]IS∼1 pM based on microdialysis [135], [136]
|
Technical issues with macromolecular measurements using microdialysis; Model overestimation of sVEGFR1-facilitated transport of VEGF; Missing blood sources of VEGF in model. |
| 77% of total plasma VEGF was sVEGFR1-complexed |
∼4% mole fraction [45]
|
Other unmodeled soluble receptors (e.g., sVEGFR2, sNRP1, plasma fibronectin) compete for VEGF in vivo. |
| 5% of total plasma sVEGFR1 was VEGF-bound |
∼0.65% mole fraction [45]
|
Other unmodeled ligands (e.g., PlGF, VEGF-B) compete for sVEGFR1 in vivo. |
| sVEGFR1 as a ligand sink negligibly reduced interstitial free VEGF while drastically elevating plasma free VEGF |
sVEGFR1 as a ligand sink lowers availability of free VEGF in vitro, ex vivo and in vivo
[8], [16], [153]
|
Computational model examined transport between tissue and blood compartments; Experimental setups examined single-compartment (e.g. pooled amniotic fluids) or relatively closed system (e.g., avascular cornea) systems. |
| sVEGFR1 did not reduce intramuscular VEGF-VEGFR2 complex formation |
sVEGFR1 is anti-angiogenic (cornea [16], pre-eclampsia [17], [18], cancer [21]–[30]) |
Current computational model neglected sVEGFR1-heterodimerization with surface VEGFRs. |
| Exercise-induced lymph flow rates elevated plasma VEGF faster than plasma sVEGFR1 |
Acute exercise quickly elevated plasma sVEGFR1, then reduced plasma VEGF [49]
|
Other exercise-induced parameter changes (e.g., hypoxia-induced sVEGFR1 production) not modeled computationally. |
