Increases in hydraulic conductance and solute permeability in a mouse model of ascending thoracic aortic aneurysm

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 which 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 ( Fbln4E57K/E57K, referred to as MU-A [aneurysm] or MU-NA [non-aneurysm]). To push the aneurysm phenotype, we also included MU mice with reduced levels of lysyl oxidase ( Fbln4E57K/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 ( Lp) 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 Lp 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 Lp 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 Lp 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.

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Increases in hydraulic conductance and solute permeability in a mouse model of ascending thoracic aortic aneurysm

Cited by 2 publications

References 31 publications

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

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

Changes in transmural mass transport correlate with ascending thoracic aortic aneurysm diameter in a fibulin-4 E57K knockin mouse model

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