Modeling of aquaporin 1-mediated transmural water transport and the resulting oncotic paradox.
Modeling of aquaporin 1-mediated transmural water transport and the resulting oncotic paradox.
复制标题
水通道蛋白 1 介导的跨壁水转运建模以及由此产生的胶体渗透悖论。
DOI：
10.1109/iembs.2011.6090241
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Rumschitzki,DavidS
中科院分区：
文献类型：
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作者：
Joshi,ShripadD;Rumschitzki,DavidS
动脉粥样硬化中最早可观察到的病变前事件，即跨血管壁的大分子运输，通过跨壁压力驱动的水运输的平流发生，其特征在于水力传导率（Lp），定义为水通量与跨壁压差的比值。水通道蛋白-1（AQP）在主动脉内皮细胞中的发现提示了水跨内皮细胞（EC）转运的新可能性，以及普遍接受的细胞旁途径。在这项研究中，我们提出了一个新的过滤理论来解释实验观察到的压力依赖性效应的水通道蛋白阻断对大鼠主动脉的脂蛋白。然而，考虑到等渗管腔，这种AQP介导的纯水流入动脉内皮下内膜（SI）应建立一个onceptide压力梯度，反对AP驱动的流动通过细胞。那么，跨AQP的流动如何能持续数小时，正如AQP实验的化学阻塞所表明的那样？为了解决这个矛盾，我们已经扩展了我们的过滤理论，也包括肿瘤活性小溶质，如白蛋白的传质。这种添加非线性地耦合质量传递、流体流动和壁力学。我们采用有限差分法，同时解决过滤和传质问题作为一个长期的解决方案的非稳态问题。我们的研究结果与实验数据一致，并建议AQP贡献约30%的现象学内皮Lp。我们还发现，由于介质过滤，在稳态下，SI中的白蛋白浓度实际上高于糖萼中的白蛋白浓度。这导致SI中较高的渗透压，其驱动流体从EC的腔侧流入SI中，而不是相反。通过AQP表达控制内皮Lp可能成为未来抑制动脉粥样硬化前事件的治疗靶点。
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.