Structural mechanisms of acute VEGF effect on microvessel permeability.
To investigate the ultrastructural mechanisms of acute microvessel hyperpermeability by vascular endothelial growth factor (VEGF), we combined a mathematical model (J Biomech Eng 116: 502-513, 1994) with experimental data of the effect of VEGF on microvessel hydraulic conductivity (L(p)) and permeability of various-sized solutes. We examined the effect of VEGF on microvessel permeability to a small solute (sodium fluorescein, Stokes radius 0.45 nm), an intermediate solute (alpha-lactalbumin, Stokes radius 2.01 nm), and a large solute [albumin (BSA), Stokes radius 3.5 nm]. Exposure to 1 nM VEGF transiently increased apparent permeability to 2.3, 3.3, and 6.2 times their baseline values for sodium fluorescein, alpha-lactalbumin, and BSA, respectively, within 30 s, and all returned to control within 2 min. On the basis of L(p) (DO Bates and FE Curry. Am J Physiol Heart Circ Physiol 271: H2520-H2528, 1996) and permeability data, the prediction from the model suggested that the most likely structural changes in the interendothelial cleft induced by VEGF would be a approximately 2.5-fold increase in its opening width and partial degradation of the surface glycocalyx.
Fu
Bingmei M
BM
Department of Mechanical Engineering, University of Nevada, Las Vegas, 89154, USA. bmfu@nscee.edu
Shen
Shang
S
D000465:Algorithms; D000818:Animals; D002138:Calibration; D002196:Capillaries / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002199:Capillary Permeability / Q000187:drug effects*; D004058:Diffusion; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007768:Lactalbumin / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D010783:Photometry; D011894:Rana pipiens; D011994:Recombinant Proteins / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012997:Solvents; D013329:Structure-Activity Relationship; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D005456:Fluorescent Dyes; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011994:Recombinant Proteins; D012997:Solvents; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012710:Serum Albumin, Bovine; D007768:Lactalbumin; D016650:Fluorescein-5-isothiocyanate