title: 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.
authors: Department of Biomedical Engineering, City College of the City University of New York, New York, New York;
authors: Tieuvi
authors: T
authors: Nguyen
authors: Department of Chemical Engineering, City College of the City University of New York, New York, New York;
authors: Jimmy
authors: J
authors: Toussaint
authors: Department of Chemical Engineering, City College of the City University of New York, New York, New York; Biology Department, City College and GSUC of The City College of New York, New York, New York; and.
authors: Yan
authors: Y
authors: Xue
authors: Department of Biomedical Engineering, City College of the City University of New York, New York, New York;
authors: Chirag
authors: C
authors: Raval
authors: Department of Biomedical Engineering, City College of the City University of New York, New York, New York;
authors: Limary
authors: L
authors: Cancel
authors: Department of Biomedical Engineering, City College of the City University of New York, New York, New York;
authors: Stewart
authors: S
authors: Russell
authors: Department of Chemical Engineering, City College of the City University of New York, New York, New York;
authors: Yixin
authors: Y
authors: Shou
authors: Department of Chemical Engineering, City College of the City University of New York, New York, New York;
authors: Omer
authors: O
authors: Sedes
authors: Department of Chemical Engineering, City College of the City University of New York, New York, New York;
authors: Yu
authors: Y
authors: Sun
authors: Department of Chemical Engineering, City College of the City University of New York, New York, New York;
authors: Roman
authors: R
authors: Yakobov
authors: Department of Biomedical Engineering, City College of the City University of New York, New York, New York;
authors: John M
authors: JM
authors: Tarbell
authors: Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York.
authors: Kung-ming
authors: KM
authors: Jan
authors: Department of Chemical Engineering, City College of the City University of New York, New York, New York; Biology Department, City College and GSUC of The City College of New York, New York, New York; and Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York david@ccny.cuny.edu.
authors: David S
authors: DS
authors: Rumschitzki
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism*; D062186:Arterial Pressure; D001692:Biological Transport; D002417:Cattle; D002478:Cells, Cultured; D004058:Diffusion; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D009997:Osmotic Pressure; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D014162:Transfection; D014867:Water / Q000378:metabolism*
chemical_list: C496022:Aqp1 protein, rat; D014867:Water; D051398:Aquaporin 1
keywords: aorta; bioengineering; endothelium; hydraulic conductivity; tracer transport; transcellular transport