Dataset Information

Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium.

ABSTRACT: Aquaporin-1, a ubiquitous water channel membrane protein, is a major contributor to cell membrane osmotic water permeability. Arteries are the physiological system where hydrostatic dominates osmotic pressure differences. In the present study, we show that the walls of large conduit arteries constitute the first example where hydrostatic pressure drives aquaporin-1-mediated transcellular/transendothelial flow. We studied cultured aortic endothelial cell monolayers and excised whole aortas of male Sprague-Dawley rats with intact and inhibited aquaporin-1 activity and with normal and knocked down aquaporin-1 expression. We subjected these systems to transmural hydrostatic pressure differences at zero osmotic pressure differences. Impaired aquaporin-1 endothelia consistently showed reduced engineering flow metrics (transendothelial water flux and hydraulic conductivity). In vitro experiments with tracers that only cross the endothelium paracellularly showed that changes in junctional transport cannot explain these reductions. Percent reductions in whole aortic wall hydraulic conductivity with either chemical blocking or knockdown of aquaporin-1 differed at low and high transmural pressures. This observation highlights how aquaporin-1 expression likely directly influences aortic wall mechanics by changing the critical transmural pressure at which its sparse subendothelial intima compresses. Such compression increases transwall flow resistance. Our endothelial and historic erythrocyte membrane aquaporin density estimates were consistent. In conclusion, aquaporin-1 significantly contributes to hydrostatic pressure-driven water transport across aortic endothelial monolayers, both in culture and in whole rat aortas. This transport, and parallel junctional flow, can dilute solutes that entered the wall paracellularly or through endothelial monolayer disruptions. Lower atherogenic precursor solute concentrations may slow their intimal entrainment kinetics.

SUBMITTER: Nguyen T

PROVIDER: S-EPMC4551120 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium.

Nguyen Tieuvi T Toussaint Jimmy J Xue Yan Y Raval Chirag C Cancel Limary L Russell Stewart S Shou Yixin Y Sedes Omer O Sun Yu Y Yakobov Roman R Tarbell John M JM Jan Kung-ming KM Rumschitzki David S DS

American journal of physiology. Heart and circulatory physiology 20150206 9

Aquaporin-1, a ubiquitous water channel membrane protein, is a major contributor to cell membrane osmotic water permeability. Arteries are the physiological system where hydrostatic dominates osmotic pressure differences. In the present study, we show that the walls of large conduit arteries constitute the first example where hydrostatic pressure drives aquaporin-1-mediated transcellular/transendothelial flow. We studied cultured aortic endothelial cell monolayers and excised whole aortas of mal ...[more]

PMID: 25659484

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Project description:Pancreatic islets of Langerhans release glucagon to maintain blood glucose levels, and release of this peptide is dysregulated in diabetes mellitus. Although the importance of proper secretion of this peptide has been shown, no measurement of its release at the single islet level has been reported. In previous work, a non-competitive assay for glucagon was developed with a 6 pM limit of detection, low enough to measure from a single islet. To incorporate this method in an online assay, a microfluidic system with several distinct features was developed. To maintain appropriate flow rates in the presence of the high concentration of salt that was required for the assay, a piezo-actuated pressure transducer with in-line flow sensors was used to drive sample flow through 80 × 50 μm (width × depth) channels, while electroosmotic flow was used to gate the sample away from 15 × 5 μm separation channel. Flow rates tested with this system were 50 - 200 nL min-1 with relative standard deviations (RSDs) ranging from 1 - 4 %. Use of the pressure-driven flow was found to increase the amount of clogs in the system, so a method to incorporate in-line filters into the channels was developed. A total of 4 low resistance, in-line microfabricated filters were evaluated, with all designs prolonging the operation time of the microfluidic device to more than 4 hours without clogs observed. Use of this system enabled highly reproducible injections (3-6% RSD). During initial incorporation of the noncompetitive assay for glucagon, it was determined that Joule heating was problematic and temperature measurements revealed the separation channel increased to more than 50°C during operation. A 3D-printed manifold was used to hold a Peltier cooler in place on the microfluidic device which produced a 2.6-fold improvement in the amount of the noncovalent glucagon complex that was detected compared to without cooling. These features are expected to be useful for not only long-term monitoring of the glucagon release from islets of Langerhans, but has the potential to be applied to a number of other microfluidic separation-based assays as well.

Dataset Information

Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium.

Publications

Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium.

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