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一种用于测定有或无动脉瘤情况下小鼠胸段升主动脉质量传输特性的多相模型。

A multiphasic model for determination of mouse ascending thoracic aorta mass transport properties with and without aneurysm.

作者信息

Kailash Keshav A, Akanda Shamimur R, Davis Alexandra L, Crandall Christie L, Castro Luis A, Setton Lori A, Wagenseil Jessica E

机构信息

Department of Biomedical Engineering, Washington University, St. Louis, MO, USA.

Department of Mechanical Engineering and Materials Science, Washington University, One Brookings Dr., CB 1185, St. Louis, MO, 63130, USA.

出版信息

Biomech Model Mechanobiol. 2025 Feb;24(1):93-105. doi: 10.1007/s10237-024-01897-5. Epub 2024 Oct 29.

Abstract

Thoracic aortic aneurysms (TAAs) are associated with aortic wall remodeling that affects transmural transport or the movement of fluid and solute across the wall. In previous work, we used a Fbln4 (MU) mouse model to investigate transmural transport changes as a function of aneurysm severity. We compared wild-type (WT), MU with no aneurysm (MU-NA), MU with aneurysm (MU-A), and MU with an additional genetic mutation that led to increased aneurysm penetrance (MU-XA). We found that all aneurysmal aortas (MU-A and MU-XA) had lower fluid flux compared to WT. Non-aneurysmal aortas (MU-NA) had higher 4 kDa FITC-dextran solute flux than WT, but aneurysmal MU-A and MU-XA aortas had solute fluxes similar to WT. Our experimental results could not isolate competing factors, such as changes in aortic geometry and solid material properties among these mouse models, to determine how intrinsic transport properties change with aneurysm severity. The objective of this study is to use biphasic and multiphasic models to identify changes in transport material properties. Our biphasic model indicates that hydraulic permeability is significantly decreased in the severe aneurysm model (MU-XA) compared to non-aneurysmal aortas (MU-NA). Our multiphasic model shows that effective solute diffusivity is increased in MU-NA aortas compared to all others. Our findings reveal changes in intrinsic transport properties that depend on aneurysm severity and are important for understanding the movement of fluids and solutes that may play a role in the diagnosis, progression, or treatment of TAA.

摘要

胸主动脉瘤(TAA)与主动脉壁重塑相关,后者会影响跨壁运输或流体及溶质在血管壁内的移动。在之前的研究中,我们使用Fbln4(MU)小鼠模型来研究跨壁运输变化与动脉瘤严重程度之间的关系。我们比较了野生型(WT)、无动脉瘤的MU(MU-NA)、有动脉瘤的MU(MU-A)以及携带额外基因突变导致动脉瘤发生率增加的MU(MU-XA)。我们发现,与WT相比,所有动脉瘤主动脉(MU-A和MU-XA)的流体通量均较低。非动脉瘤主动脉(MU-NA)的4 kDa FITC-葡聚糖溶质通量高于WT,但动脉瘤的MU-A和MU-XA主动脉的溶质通量与WT相似。我们的实验结果无法分离这些小鼠模型中相互竞争的因素,如主动脉几何形状和固体材料特性的变化,以确定内在运输特性如何随动脉瘤严重程度而改变。本研究的目的是使用双相和多相模型来识别运输材料特性的变化。我们的双相模型表明,与非动脉瘤主动脉(MU-NA)相比,严重动脉瘤模型(MU-XA)的水力传导率显著降低。我们的多相模型显示,与其他所有模型相比,MU-NA主动脉的有效溶质扩散率增加。我们的研究结果揭示了内在运输特性的变化,这些变化取决于动脉瘤的严重程度,对于理解可能在TAA的诊断、进展或治疗中起作用的流体和溶质的移动非常重要。

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