| Autor: |
Crandall CL; Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, Missouri, United States., Wu Y; Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, Missouri, United States., Kailash KA; Department of Biomedical Engineering, Washington University, St. Louis, Missouri, United States., Bersi MR; Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, Missouri, United States., Halabi CM; Pediatric Nephrology, Washington University School of Medicine, St. Louis, Missouri, United States., Wagenseil JE; Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, Missouri, United States. |
| Abstrakt: |
Thoracic aortic aneurysm is characterized by dilation of the aortic diameter by greater than 50%, which can lead to dissection or rupture. Common histopathology includes extracellular matrix remodeling that may affect transmural mass transport, defined as the movement of fluids and solutes across the wall. We measured in vitro ascending thoracic aorta mass transport in a mouse model with partial aneurysm phenotype penetration due to a mutation in the extracellular matrix protein fibulin-4 [ Fbln4 E57K/E57K , referred to as MU-A (aneurysm) or MU-NA (no aneurysm)]. To push the aneurysm phenotype, we also included MU mice with reduced levels of lysyl oxidase [ Fbln4 E57K/E57K ;Lox +/- , referred to as MU-XA (extreme aneurysm)] and compared all groups to wild-type (WT) littermates. The phenotype variation allows investigation of how aneurysm severity correlates with mass transport parameters and extracellular matrix organization. We found that MU-NA ascending thoracic aortae have similar hydraulic conductance ( L p ) to WT, but 397% higher solute permeability (ω) for 4 kDa FITC-dextran. In contrast, MU-A and MU-XA ascending thoracic aortae have 44-68% lower L p and similar ω to WT. The results suggest that ascending thoracic aortic aneurysm progression involves an initial increase in ω, followed by a decrease in L p after the aneurysm has formed. All MU ascending thoracic aortae are longer and have increased elastic fiber fragmentation in the extracellular matrix. There is a negative correlation between diameter and L p or ω in MU ascending thoracic aortae. Changes in mass transport due to elastic fiber fragmentation could contribute to aneurysm progression or be leveraged for treatment. NEW & NOTEWORTHY Transmural mass transport is quantified in the ascending thoracic aorta of mice with a mutation in fibulin-4 that is associated with thoracic aortic aneurysms. Fluid and solute transport depend on aneurysm severity, correlate with elastic fiber fragmentation, and may be affected by proteoglycan deposition. Transport properties of the ascending thoracic aorta are provided and can be used in computational models. The changes in mass transport may contribute to aneurysm progression or be leveraged for aneurysm treatment. |
