The Presence of VEGF Receptors on the Luminal Surface of Endothelial Cells Affects VEGF Distribution and VEGF Signaling
Figure 4
Flow diagrams for a fixed concentration of free VEGF in the plasma.
A. The inflows and outflows are expressed in pmoles/s. The density of luminal and abluminal receptors was varied from 0 to 10,000 per endothelial cell. Free VEGF concentration in the plasma was fixed at 1 pM for a vascular permeability of 4×10−8 cm/s. From top left, counter-clockwise: i. VEGF secreted per parenchymal cell; ii. free VEGF concentration in the tissue (in pM); iii. VEGF intravasating; iv. VEGF disappearing through internalization of the luminal receptors to which it binds; v. VEGF drained through the lymphatics; vi. VEGF disappearing through internalization of abluminal receptors to which it binds. VEGF extravasating and VEGF cleared from the plasma are constant over the course of the simulations due to the fixed free VEGF concentration in the plasma and equal to 2.65×10−4 and 2.94×10−3 pmoles/s respectively. The yellow dot corresponds to the configuration of 10,000 abluminal receptors and no luminal receptors. The purple dot identifies an equal density of receptors on luminal and abluminal surfaces of the endothelial cells (5,000 receptors on each side per endothelial cell). The green dot corresponds to the case of 10,000 luminal receptors and no abluminal receptors. B. Flows normalized to VEGF secretion for different luminal receptor densities: i. no abluminal receptors; ii. 500 abluminal receptors per EC; iii. 1,000 abluminal receptors per EC; iv. 10,000 abluminal receptors per EC. EC = endothelial cell.