Lucotte Bertrand M, Powell Chloe, Knutson Jay R, Combs Christian A, Malide Daniela, Yu Zu-Xi, Knepper Mark, Patel Keval D, Pielach Anna, Johnson Errin, Borysova Lyudmyla, Dora Kim A, Balaban Robert S
Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892.
Vascular Pharmacology Research Group, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom.
Proc Natl Acad Sci U S A. 2017 May 2;114(18):4805-4810. doi: 10.1073/pnas.1620008114. Epub 2017 Apr 3.
The artery wall is equipped with a water permeation barrier that allows blood to flow at high pressure without significant water leak. The precise location of this barrier is unknown despite its importance in vascular function and its contribution to many vascular complications when it is compromised. Herein we map the water permeability in intact arteries, using coherent anti-Stokes Raman scattering (CARS) microscopy and isotopic perfusion experiments. Generation of the CARS signal is optimized for water imaging with broadband excitation. We identify the water permeation barrier as the endothelial basolateral membrane and show that the apical membrane is highly permeable. This is confirmed by the distribution of the AQP1 water channel within endothelial membranes. These results indicate that arterial pressure equilibrates within the endothelium and is transmitted to the supporting basement membrane and internal elastic lamina macromolecules with minimal deformation of the sensitive endothelial cell. Disruption of this pressure transmission could contribute to endothelial cell dysfunction in various pathologies.
动脉壁配备有透水屏障,可使血液在高压下流动而不会出现明显的水渗漏。尽管这种屏障在血管功能中很重要,且当其受损时会导致许多血管并发症,但其确切位置尚不清楚。在此,我们使用相干反斯托克斯拉曼散射(CARS)显微镜和同位素灌注实验来绘制完整动脉中的水渗透性。CARS信号的产生针对宽带激发的水成像进行了优化。我们确定水渗透屏障为内皮细胞基底外侧膜,并表明顶端膜具有高渗透性。这通过内皮细胞膜内水通道蛋白1(AQP1)水通道的分布得到证实。这些结果表明,动脉压力在内皮细胞内达到平衡,并以敏感内皮细胞最小程度的变形传递到支持性基底膜和内弹性膜大分子。这种压力传递的破坏可能导致各种病理状态下的内皮细胞功能障碍。