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

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^E57K/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.