Increases in hydraulic conductance and solute permeability in a mouse model of ascending thoracic aortic aneurysm. (December 2022)

• Record Type: Journal Article
• Authors: Crandall, Christie L.; Kim, Sean Y.; Rother, Jacob; Lee, Vivian S.; Mecham, Robert P.; Wagenseil, Jessica E.
• Is Part Of: Journal of biomechanics. Volume 145(2022)
• Publication Date: 2022-12
• Subjects: Elastin -- Diffusion -- Solute -- Mass transport -- Lysyl oxidase -- Thoracic aortic aneurysm; TAA thoracic aortic aneurysm -- IEL internal elastic lamina -- LOX lysyl oxidase -- WT wild-type -- ATA ascending thoracic aorta -- PBS phosphate buffered saline -- SMC smooth muscle cell -- EC endothelial cell -- PG proteoglycan -- MMP matrix metalloproteinase; Animal mechanics -- Periodicals; Biomechanics -- Periodicals; Biomechanics -- Periodicals; Mécanique animale -- Périodiques; Biomécanique -- Périodiques; Electronic journals; 571.4305
• DOI: 10.1016/j.jbiomech.2022.111360
• Languages: English
• ISSNs: 0021-9290

Abstract

Abstract: Large elastic arteries, such as the aorta, contain concentric layers of elastic laminae composed mainly of the extracellular matrix protein elastin. The structure of the elastic laminae could affect transmural mass transport and contribute to aortic disease progression. We studied the effects of a genetic mutation ( Lox M292R/+, referred to as MU) in mice associated with ascending thoracic aortic aneurysm (TAA) on the mass transport and elastic laminae structure. Solute absent fluid flux and hydraulic conductance through the ascending aortic wall were not significantly different between groups, however solute present fluid flux, hydraulic conductance, solute flux, and solute permeability of 4 kDa FITC-dextran were significantly increased in the MU group, indicating that movement of small molecules into the aortic wall is facilitated in MU mice. Quantification from light microscopy images of the ascending aorta showed no significant differences in wall thickness, or inner elastic lamina fenestration size and density, but an increase in the number of elastic laminae breaks in the MU group. Ultrastructural comparisons from transmission electron micrographs suggest less dense and disorganized elastic laminae in MU aorta that may also contribute to the transport differences. Our results provide an initial investigation into the connections between mass transport and elastic laminae structure, specifically in a genetic mouse aneurysm model, which can be further used to understand TAA pathology and develop treatment strategies.