Is the transcellular pathway is an important contributor to water flow across rat aortic endothelium

摘要

Plasma, mostly water and solutes, advects low-density-lipoprotein (LDL) across the arterial endothelium. Subendothelial LDL deposition triggers pre-artherogenic lesion formation. This water flux is believed to occur paracellularly. We investigate the potential significance of the transcelluar pathway through the ubiquitous aquaporin-1 (AQP1) water channel protein to total transmural water flow. AQP1 downregulation by means of small interference RNA (siRNA) induces a significant decrease in Rat aortic endothelial cells (RAECs) permeability to water and small solutes in vitro. In vitro water flux (Jv) decreased by 56.4%. This large reduction is likely only partially due to the direct effects of the suppressing the transcellular AQP1 pathway. Suppression of this pathway increases flow resistance, likely causing the transmural pressure to compresses the cells against the rigid support and increases cell-cell overlap, which likely acocunts for the balance of the Lp reduction. A study of RAEC permeability to tetramethylrhodamine (TAMRA) and tetramethyl-rhodamine-iso-thiocyanate (TRITC)-albumin, solutes traverse only the cell-cell junctions, provides evidence consistent with this interpretation. AQP1's suppression led to a 21.6% drop in TAMRA permeability and a 26.3%/16.5% drop in albumin permeability under convection/diffusion respectively, consistent with increased cell-cell overlap. AQP1, might affect lipid transport in a beneficial way with regard to disease progression.