The effect of varying albumin concentration and hydrostatic pressure on hydraulic conductivity and albumin permeability of cultured endothelial monolayers

Dull, Randal O.; Jo, Hanjoong; Sill, Howard W.; Hollis, Theodore M.; Tarbell, John M.

doi:10.1016/0026-2862(91)90037-c

Cited by 75 publications

(59 citation statements)

References 25 publications

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“…There have been no previous studies of convective (pressurized) transport of LDL in vitro. The water flux values induced by a 10-cmH 2 O pressure differential that were observed in this study (Tables 1 and 3) are comparable to previous in vitro studies and are of the same order of magnitude as fluxes across the aorta of rabbits at physiological pressures (7).…”

Section: Discussionsupporting

confidence: 90%

In vitro study of LDL transport under pressurized (convective) conditions

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Fitting²,

Tarbell³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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It is difficult to assess the transport pathways that carry low-density lipoprotein (LDL) into the artery wall in vivo, and there has been no previous in vitro study that has examined transendothelial transport under physiologically relevant pressurized (convective) conditions. Therefore, we measured water, albumin, and LDL fluxes across bovine aortic endothelial cell (BAEC) monolayers in vitro and determined the relative contributions of vesicles, paracellular transport through “breaks” in the tight junction, and “leaky” junctions associated with dying or dividing cells. Our results show that leaky junctions are the dominant pathway for LDL transport (>90%) under convective conditions and that albumin also has a significant component of transport through leaky junctions (44%). Transcellular transport of LDL by receptor-mediated processes makes a minor contribution (<10%) to overall transport under convective conditions.

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Section: Discussionsupporting

confidence: 90%

In vitro study of LDL transport under pressurized (convective) conditions

Cancel

Fitting²,

Tarbell³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…4. Of interest, the absolute values of are from 2 to 10 times lower than those reported in cultured cell models with continuous endothelium (8,9,12,18,61).…”

Section: Pathways For Transvascular Macromolecule Exchangementioning

confidence: 80%

Sexual dimorphism in the permeability response of coronary microvessels to adenosine

Huxley

Wang

Whitt

2005

American Journal of Physiology-Heart and Circulatory Physiology

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Gender influences volume regulation via several mechanisms; whether these include microvascular exchange, especially in the heart, is not known. In response to adenosine (Ado), permeability (P s )to protein of coronary arterioles of female pigs decreases acutely. Whether Ado induces similar P s changes in arterioles from males or whether equivalent responses occur in coronary venules of either sex has not been determined. Hypotheses that 1) basal P s properties and 2) P s responses to vasoactive stimuli are sex independent were evaluated from measures of P s to two hydrophilic proteins, α-lactalbumin and porcine serum albumin (PSA), in arterioles and venules isolated from hearts of adult male and female pigs. Consistent with hypothesis 1, basal P s values of both microvessel types were independent of sex. Contrary to hypothesis 2, P s responses to Ado varied with sex, protein, and vessel type. Confirming earlier studies, Ado induced a ~20% decrease in P s to both proteins in coronary arterioles from females. In arterioles from males, Ado did not change P s for α-lactalbumin ( , 3 ± 13%) whereas P s for PSA ( ) decreased by 27 ± 8% (P < 0.005). In venules from females, Ado elevated by 44 ± 20% (P < 0.05), whereas in those from males, Ado reduced by 24 ± 5% (P < 0.05). The variety of outcomes is consistent with transvascular protein and protein-carried solute flux being regulated by multiple sex-dependent mechanisms in the heart and provides evidence of differences in exchange homeostasis of males and females in health and, likely, disease.

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“…Hence, the extent of extravasation of albumin may be reduced by increasing its molecular size. It has also been shown that albumin, with an estimated radius of 35.5 Å, and water do not share a common pathway in crossing the endothelial monolayer, suggesting the existence of a large pore pathway for albumin (Dull et al, 1991). Namely, the increase in the molecular size of HSA clearly led to retardation in extravasation through the vascular endothelium, resulting in a longer lifetime in the blood stream.…”

Section: Discussionmentioning

confidence: 99%

Superior Plasma Retention of a Cross-Linked Human Serum Albumin Dimer in Nephrotic Rats as a New Type of Plasma Expander

Taguchi

Urata²,

Anraku³

et al. 2010

Drug Metabolism and Disposition

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ABSTRACT:Human serum albumin (HSA) is used clinically as a plasma expander in patients with hypoalbuminemia and can also function as a drug carrier. However, the administered HSA is readily eliminated from the blood circulation under pathological conditions, especially the nephrotic syndrome. In this study, we present data on the pharmacokinetics of a structurally defined HSA dimer [two HSA molecules that are cross-linked by reaction with 1,6-bis(maleimido)hexane via Cys34] in nephrotic rats and its superior circulation persistence, owing to the molecular size effect. The half-time (t 1/2 ) of the HSA dimer persisted in the circulation 1.3 times longer than that of monomeric HSA in normal rats, primarily because of the suppression of the accumulation of the HSA dimer in the skin and muscle. In nephrotic rats, the t 1/2 of the HSA monomer decreased considerably, whereas the HSA dimer remained unaltered in the blood stream, similar to that for normal rats. As a result, the t 1/2 of the HSA dimer was 2-fold longer than that of the HSA monomer. This longer t 1/2 can be attributed to the fact that accumulation in the kidney and urinary excretion of the HSA dimer were significantly suppressed. The cross-linked HSA dimer shows a longer blood circulation than native HSA monomer in nephrotic rats, which can be attributed to the suppression of renal filtration and leakage into the extravascular space. This HSA dimer has the potential for use as a drug carrier, new plasma expander, and an artificial albumin-based oxygen carrier under a high glomerular permeability condition such as nephrosis.

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The effect of varying albumin concentration and hydrostatic pressure on hydraulic conductivity and albumin permeability of cultured endothelial monolayers

Cited by 75 publications

References 25 publications

In vitro study of LDL transport under pressurized (convective) conditions

In vitro study of LDL transport under pressurized (convective) conditions

Sexual dimorphism in the permeability response of coronary microvessels to adenosine

Superior Plasma Retention of a Cross-Linked Human Serum Albumin Dimer in Nephrotic Rats as a New Type of Plasma Expander

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