Structural Mechanisms in the Abolishment of VEGF-Induced Microvascular Hyperpermeability by cAMP

Authors

Bingmei M. Fu, City University of New YorkFollow
Shang Shen, University of Nevada, Las Vegas
Bin Chen, University of Nevada, Las Vegas

Document Type

Article

Publication Date

6-2006

Publication Title

Journal of Biomechanical Engineering

Volume

128

Issue

3

First page number:

317

Last page number:

328

Abstract

To investigate the structural mechanisms by which elevation of the intraendothelial cAMP levels abolishes or attenuates the transient increase in microvascular permeability by vascular endothelial growth factor (VEGF), we examined cAMP effect on VEGF induced hyperpermeability to small solute sodium fluorescein (Stokes radius=0.45 nm) P^{sodium fluorescein}, intermediate-sized solute a-lactalbumin (Stokes radius=2.01 nm) P^{a-lactalbumin}, and large solute albumin (BSA, Stokes radius=3.5 nm) PBSA on individually perfused microvessels of frog mesenteries. After 20 min pretreatment of 2 mM cAMP analog, 8-bromo-cAMP, the initial increase by 1 nM VEGF was completely abolished in P^{sodium fluorescein} (from a peak increase of 2.6±0.37 times control with VEGF alone to 0.96±0.07 times control with VEGF and cAMP), in P ^{a-lactalbumin} (from a peak increase of 2.7±0.33 times control with VEGF alone to 0.76±0.07 times control with VEGF and cAMP), and in PBSA (from a peak increase of 6.5±1.0 times control with VEGF alone to 0.97±0.08 times control with VEGF and cAMP). Based on these measured data, the prediction from our mathematical models suggested that the increase in the number of tight junction strands in the cleft between endothelial cells forming the microvessel wall is one of the mechanisms for the abolishment of VEGF-induced hyperpermeability by cAMP.

Keywords

Blood-vessels; Cells – Permeability; Cyclic adenosine monophosphate; Vascular endothelial growth factors

Disciplines

Biomechanics and Biotransport | Biomedical Engineering and Bioengineering | Engineering | Molecular, Cellular, and Tissue Engineering

Language

English

Permissions

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Repository Citation

Fu, B. M., Shen, S., Chen, B. (2006). Structural Mechanisms in the Abolishment of VEGF-Induced Microvascular Hyperpermeability by cAMP. Journal of Biomechanical Engineering, 128(3), 317-328.