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

IF 3 3区 医学 Q2 BIOPHYSICS Biomechanics and Modeling in Mechanobiology Pub Date : 2024-10-29 DOI:10.1007/s10237-024-01897-5
Keshav A Kailash, Shamimur R Akanda, Alexandra L Davis, Christie L Crandall, Luis A Castro, Lori A Setton, Jessica E Wagenseil
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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 Fbln4E57K/E57K (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.

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用于确定有无动脉瘤的小鼠升胸主动脉质量传输特性的多相模型。
胸主动脉瘤(TAA)与主动脉壁重塑有关,重塑会影响壁间转运或流体和溶质的跨壁运动。在之前的工作中,我们使用 Fbln4E57K/E57K (MU) 小鼠模型研究了跨壁运输变化与动脉瘤严重程度的关系。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)和有额外基因突变导致动脉瘤穿透性增加的 MU(MU-XA)。我们发现,与 WT 相比,所有动脉瘤主动脉(MU-A 和 MU-XA)的流体通量都较低。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 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隔离这些小鼠模型之间的竞争因素,如主动脉几何形状和固体材料特性的变化,从而确定内在运输特性如何随动脉瘤严重程度而变化。本研究的目的是使用双相和多相模型来确定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)的水力渗透性明显下降。我们的多相模型显示,MU-NA 主动脉的有效溶质扩散率比其他所有主动脉都要高。我们的研究结果揭示了取决于动脉瘤严重程度的内在运输特性的变化,这对了解可能在 TAA 的诊断、进展或治疗中发挥作用的液体和溶质的运动非常重要。
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来源期刊
Biomechanics and Modeling in Mechanobiology
Biomechanics and Modeling in Mechanobiology 工程技术-工程:生物医学
CiteScore
7.10
自引率
8.60%
发文量
119
审稿时长
6 months
期刊介绍: Mechanics regulates biological processes at the molecular, cellular, tissue, organ, and organism levels. A goal of this journal is to promote basic and applied research that integrates the expanding knowledge-bases in the allied fields of biomechanics and mechanobiology. Approaches may be experimental, theoretical, or computational; they may address phenomena at the nano, micro, or macrolevels. Of particular interest are investigations that (1) quantify the mechanical environment in which cells and matrix function in health, disease, or injury, (2) identify and quantify mechanosensitive responses and their mechanisms, (3) detail inter-relations between mechanics and biological processes such as growth, remodeling, adaptation, and repair, and (4) report discoveries that advance therapeutic and diagnostic procedures. Especially encouraged are analytical and computational models based on solid mechanics, fluid mechanics, or thermomechanics, and their interactions; also encouraged are reports of new experimental methods that expand measurement capabilities and new mathematical methods that facilitate analysis.
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