A VEGF165-induced phenotypic switch from increased vessel density to increased vessel diameter and increased endothelial NOS activity
| Autor: | Unni M. Chandrasekharan, Terri L. McKay, Patricia Parsons-Wingerter, Krishnan Radhakrishnan, Paul E. DiCorleto, Andrew G. Farr, Brian Albarran |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Nitric Oxide Synthase Type III Angiogenesis Neovascularization Physiologic Coturnix Endothelial NOS Biochemistry Chorioallantoic Membrane Nitric oxide chemistry.chemical_compound Enos biology.animal Internal medicine medicine Image Processing Computer-Assisted Animals Humans biology Dose-Response Relationship Drug Cell Biology Anatomy Arteries biology.organism_classification Phenotype Quail Recombinant Proteins Vessel diameter Chorioallantoic membrane Endocrinology chemistry Endothelium Vascular Cardiology and Cardiovascular Medicine |
| Zdroj: | Microvascular research. 72(3) |
| ISSN: | 0026-2862 |
| Popis: | Although vascular endothelial growth factor-165 (VEGF 165 ) regulates numerous angiogenic cellular activities, its complex effects on vascular morphology are not highly quantified. By fractal-based, multiparametric branching analysis of 2D vascular pattern in the quail chorioallantoic membrane (CAM), we report that vessel density increased maximally at lower VEGF concentrations, but that vessel diameter and activity of endothelial nitric oxide synthase (eNOS) increased maximally at higher VEGF concentrations. Following exogenous application of human VEGF 165 to the CAM at embryonic day 7, vessel density and diameter were measured after 24 h at arterial end points by the fractal dimension ( D f ) and generational branching parameters for vessel area density ( A v ), vessel length density ( L v ) and vessel diameter ( D v ) using the computer code VESGEN. The VEGF-dependent phenotypic switch from normal vessels displaying increased vessel density to abnormal, dilated vessels typical of tumor vasculature and other pathologies resulted from an approximate threefold increase in VEGF concentration (1.25 to 5 μg/CAM) and correlated positively with increased eNOS activity. Relative to control specimens, eNOS activity increased maximally to 60% following VEGF treatment at 5 μg/CAM, compared to 10% at 1.25 μg/CAM, and was accompanied by no significant change in activity of inducible NOS. In summary, VEGF 165 induced a phenotypic switch from increased vessel density associated with low VEGF concentration, to increased vessel diameter and increased eNOS activity at high VEGF concentration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect