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Figure 7 | BMC Systems Biology

Figure 7

From: A compartment model of VEGF distribution in blood, healthy and diseased tissues

Figure 7

Flows of VEGF in the body at steady state. The flows are normalized to the moles of VEGF secreted per unit time in the normal tissue. Units before normalization: moles/s. VEGF165 secretion rate in healthy tissue q N = 0.102 molecule/cell/s; VEGFR1 = 10,000, VEGFR2 = 10,000 molecules/endothelial cell; NRP1 = 10,000 molecules/endothelial cell in the healthy tissue. A, In the absence of diseased tissue and clearance, the internalization of VEGF balances the secretion. There is no net flow between the two compartments. Vascular permeability of the healthy tissue, k p N MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4AaS2aa0baaSqaaiabdchaWbqaaiabd6eaobaaaaa@2FEF@ = 4 × 10-8 cm/s; B, In the presence of a tumor and of VEGF clearance, most VEGF that has been secreted is internalized after binding to receptors (99.866%). A small fraction penetrates the bloodstream. Most of VEGF secreted in the tumor is being internalized after binding to receptors (99.150%). This configuration corresponds to low vascular permeability in healthy tissue in Figure 4D. The diseased compartment represents a 4-cm diameter tumor; vascular permeability of the healthy tissue, k p N MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4AaS2aa0baaSqaaiabdchaWbqaaiabd6eaobaaaaa@2FEF@ = 4 × 10-8 cm/s; vascular permeability in the tumor k p D MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4AaS2aa0baaSqaaiabdchaWbqaaiabdseaebaaaaa@2FDB@ = 4 × 10-7 cm/s; VEGF165 secretion rate in tumor q D = 0.076 molecule/cell/s; VEGF plasma clearance c V = 0.0206 min-1 [28]; NRP1 = 100,000 molecules/endothelial cell in the tumor. C, At higher vascular permeability in the healthy tissue k p N MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4AaS2aa0baaSqaaiabdchaWbqaaiabd6eaobaaaaa@2FEF@ = 4 × 10-6 cm/s, the net flow of VEGF entering the bloodstream from the healthy tissue increases to 0.580%. The internalization of receptors in the healthy tissue decreases (99.420%) while the internalization of receptors in the tumor increases (99.861%). This configuration corresponds to high vascular permeability in healthy tissue in Figure 4D. The diseased compartment represents a 4-cm diameter tumor; vascular permeability k p D MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4AaS2aa0baaSqaaiabdchaWbqaaiabdseaebaaaaa@2FDB@ = 4 × 10-7 cm/s in the tumor and k p N MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4AaS2aa0baaSqaaiabdchaWbqaaiabd6eaobaaaaa@2FEF@ = 4 × 10-8 cm/s in healthy tissue; VEGF165 secretion rate in tumor q D = 0.076 molecule/cell/s; VEGF plasma clearance c V = 0.0206 min-1; NRP1 = 100,000 molecules/endothelial cell in the tumor.

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