Biomedical subjects

Bingmei M Fu

Publications and source records attributed to Bingmei M Fu.

8 recordsLinked to original sources

PubMed2006

Structural mechanisms in the abolishment of VEGF-induced microvascular hyperpermeability by cAMP.

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 alpha-lactalbumin (Stokes radius = 2.01 nm) P(alpha-lactalbumin), and large solute albumin (BSA, Stokes radius = 3.5 nm) P(BSA) 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(alpha-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 P(BSA) (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.

Animals↗

PubMed2005

Determination of microvessel permeability and tissue diffusion coefficient of solutes by laser scanning confocal microscopy.

Interstitium contains a matrix of fibrous molecules that creates considerable resistance to water and solutes in series with the microvessel wall. On the basis of our preliminary studies, by using laser-scanning confocal microscopy and a theoretical model for interstitial transport, we determined both microvessel solute permeability (P) and solute tissue diffusion coefficient (D) of alpha-lactalbumin (Stokes radius 2.01 nm) from the rate of tissue solute accumulation and the radial concentration gradient around individually perfused microvessel in frog mesentery. P(alpha-lactalbumin) is 1.7 +/- 0.7(SD) x 10(-6) cm/s (n = 6). D(t)/D(free) for alpha-lactalbumin is 27% +/- 5% (SD) (n = 6). This value of D(t)/D(free) is comparable to that for small solute sodium fluorescein (Stokes radius 0.45 nm), while p(alpha-lactalbumin) is only 3.4% of p(sodium fluorescein). Our results suggest that frog mesenteric tissue is much less selective to solutes than the microvessel wall.

Animals↗

PubMed2004

Acute VEGF effect on solute permeability of mammalian microvessels in vivo.

To investigate the effect of vascular endothelial growth factor (VEGF) on solute permeability of mammalian microvessels, we measured the apparent permeability (P) of various-sized solutes on the postcapillary venules of rat mesentery in vivo. Exposure to 1 nM VEGF transiently increased P from a mean of 1.4 (+/-0.11 SE, n = 17) to a peak of 2.8 (+/-0.28 SE) x 10(-5) cm/s, a 2.4-fold increase for small solute sodium fluorescein (Stokes radius 0.45 nm), from a mean of 0.44 (+/-0.05 SE, n = 16) to a peak of 1.5 (+/-0.19 SE) x 10(-)5 cm/s, a 3.6-fold increase for intermediate-sized solute alpha-lactalbumin (Stokes radius 2.01 nm), from a mean of 0.049 (+/-0.0032 SE, n = 16) to a peak of 0.36 (+/-0.032 SE) x 10(-5) cm/s, a 7.9-fold increase for large solute bovine serum albumin (Stokes radius 3.55 nm), within 30 s. In approximately 2 min, all increased P returned to the baseline values. The response pattern of P to VEGF and the ratios of the peak to control values for rat mesenteric microvessels are similar to those of frog mesenteric microvessels [Am. J. Physiol.: Heart Circ. Physiol. 284 (2003) H2124]. Instead of considerable heterogeneity in the frog mesenteric microvessels, the acute response to 1 nM VEGF is homogeneous in the rat mesenteric microvessels.

Animals↗

PubMed2004

An electrodiffusion-filtration model for effects of endothelial surface glycocalyx on microvessel permeability to macromolecules.

Endothelial surface glycocalyx plays an important role in the regulation of microvessel permeability by possibly changing its charge and configuration. To investigate the mechanisms by which surface properties of the endothelial cells control the changes in microvessel permeability, we extended the electrodiffusion model developed by Fu et al. [Am. J. Physiol. 284, H1240-1250 (2003)], which is for the interendothelial cleft with a negatively charged surface glycocalyx layer, to include the filtration due to hydrostatic and oncotic pressures across the microvessel wall as well as the electrical potential across the glycocalyx layer On the basis of the hypotheses proposed by Curry [Microcirculation 1(1): 11-26 (1994)], the predictions from this electrodiffusion-filtration model provide a good agreement with experimental data for permeability of negatively charged a-lactalbumin summarized in Curry [Microcirculation 1(1), 11-26 (1994)] under various conditions. In addition, we applied this new model to describe the transport of negatively charged macromolecules, bovine serum albumin (BSA), across venular microvessels in frog mesentery. According to the model, the convective component of the albumin transport is greatly diminished by the presence of a negatively charged glycocalyx under both normal and increased permeability conditions.

Animals↗

PubMed2003

A two-barrier compartment model for volume flow across amphibian skin.

The amphibian skin has long been used as a model tissue for the study of ion transport and osmotic water movement across tight epithelia. To understand the mechanism of water uptake across amphibian skin, we model the skin as a well-stirred compartment bounded by an apical barrier and a tissue barrier. The compartment represents the lateral intercellular space between cells in the stratum granulosum. The apical barrier represents the stratum corneum, the principal/mitochondria-rich cells, and the junctional area between cells. This barrier is hypothesized to have the ability to actively transport solutes through Na+-K+-ATPase. The actively transported solute flux is assumed to satisfy the Michaelis-Menten relationship. The tissue barrier represents a composite barrier comprising the stratum spinosum, the stratum germinativum, the basal lamina, and the dermis. Our model shows that 1) the predicted rehydration rates from apical bathing solutions are in good agreement with the experiment results in Hillyard and Larsen (J Comp Physiol 171: 283-292, 2001); 2) under their experimental conditions, there is a substantial volume flux coupled to the active solute flux and this coupled volume flux is nearly constant when the osmolality of the apical bathing solution is >100 mosmol/kgH2O; 3) the molar ratio of the actively transported solute flux to the coupled water flux is about 1:160, which is the same as that reported in Nielsen (J Membr Biol 159: 61-69, 1997).

Animals↗

PubMed2003

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.

Algorithms↗

PubMed2003

A model for the modulation of microvessel permeability by junction strands.

To investigate the effect of junction strands on microvessel permeability, we extend the previous analytical model developed by Fu et al. (1994, J. Biomech. Eng., 116, pp. 502-513), for the interendothelial cleft to include multiple junction strands in the cleft and an interface between the surface glycocalyx layer and the cleft entrance. Based on the electron microscopic observations by Adamson et al. (1998, Am. J. Physiol., 274(43), pp. H1885-H1894), that elevation of intracellular cAMP levels would increase number of tight junction strands, this two-junction-strand and two-pore model can successfully account for the experimental data for the decreased permeability to water, small and intermediate-sized solutes by cAMP.

Animals↗

PubMed2002

An electrodiffusion model for effects of surface glycocalyx layer on microvessel permeability.

To investigate the charge effect of the endothelial surface glycocalyx on microvessel permeability, we extended the three-dimensional model developed by Fu et al. (J Biomech Eng 116: 502-513, 1994) for the interendothelial cleft to include a negatively charged glycocalyx layer at the entrance of the cleft. Both electrostatic and steric exclusions on charged solutes were considered within the glycocalyx layer and at the interfaces. Four charge-density profiles were assumed for the glycocalyx layer. Our model indicates that the overall solute permeability across the microvessel wall including the surface glycocalyx layer and the cleft region is independent of the charge-density profiles as long as they have the same maximum value and the same total charge. On the basis of experimental data, this model predicts that the charge density would be 25-35 meq/l in the glycolcalyx of frog mesenteric capillaries. An intriguing prediction of this model is that when the concentrations of cations and anions are unequal in the lumen due to the presence of negatively charged proteins, the negatively charged glycocalyx would provide more resistance to positively charged solutes than to negatively charged ones.

Capillary Permeability↗