title: Modeling of aquaporin 1-mediated transmural water transport and the resulting oncotic paradox.
abstract: The earliest observable prelesion event in atherosclerosis, macromolecular transport across the vessel wall, occurs via advection by transmural pressure-driven water transport, characterized by the hydraulic conductivity (Lp), defined as the ratio of water flux to the transmural pressure difference. The discovery of the presence of aquaporin-1 (AQP) in aortic endothelial cells suggests a new possibility of water transport across the endothelial cell (EC), alongside the generally accepted paracellular route. In this study, we propose a new filtration theory to explain the experimentally observed pressure-dependent effect of AQP-blocking on the Lp of rat aorta. However, given the isotonic lumen, this AQP-mediated pure water inflow into the arterial subendothelial intima (SI) should set up an oncotic pressure gradient that opposes the AP-driven flow through the cell. How then could trans-AQP flow persist for many hours, as indicated by chemical blocking of AQP experiments? To resolve this paradox, we have extended our filtration theory to also include the mass transfer of oncatically active small solutes like albumin. This addition non-linearly couples the mass transfer, the fluid flow and the wall mechanics. We employ finite difference methods to simultaneously solve the filtration and mass-transfer problem as a long-time solution of an unsteady problem. Our results agree well with the experimental data and suggest that AQPs contribute about 30% to the phenomenological endothelial Lp. We have also found that, due to media filtration, at steady state, the albumin concentration in the SI is in fact higher than in the glycocalyx. This results in higher osmotic pressure in the SI, which drives the fluid flow into the SI from the luminal side of the EC and not the other way around. Controlling endothelial Lp, via AQP expression, might serve as a future therapeutic target to inhibit pre-atherosclerotic events.
authors.affiliation: Department of Chemical Engineering, The City College of New York, New York, NY 10031, USA. sjoshi@che.ccny.cuny.edu
authors.forename: Shripad D
authors.initials: SD
authors.lastname: Joshi
authors.forename: David S
authors.initials: DS
authors.lastname: Rumschitzki
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism*; D001158:Arteries / Q000502:physiology*; D001693:Biological Transport, Active / Q000502:physiology; D001834:Body Water / Q000378:metabolism*; D003198:Computer Simulation; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008955:Models, Cardiovascular; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D012709:Serum Albumin; D051398:Aquaporin 1