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Elastic fiber fragmentation increases transmural hydraulic conductance and solute transport in mouse arteries.
Journal of Biomechanical Engineering 2018 December 6
Transmural advective transport of solute and fluid was investigated in mouse carotid arteries with either a genetic knockout of Fibulin-5 (Fbln5-/-) or treatment with elastase to determine the influence of a disrupted elastic fiber matrix on wall transport properties. Fibulin-5 is an important director of elastic fiber assembly. Arteries from Fbln5-/- mice have a loose, non-continuous elastic fiber network and were hypothesized to have reduced resistance to advective transport. Experiments were carried out ex vivo at physiological pressure and axial stretch. Hydraulic conductance (Lp ) was measured to be 4.99·10-6 ± 8.94·10-7, 3.18·-5 ± 1.13·10-5 (P < 0.01), and 3.57·10-5 ± 1.77·10-5 (P < 0.01) mm·s-1·mmHg-1 for wild-type, Fbln5-/-, and elastase-treated carotids, respectively. Solute fluxes of 4, 70, and 150 kDa FITC-dextran were statistically increased in Fbln5-/- compared to wild-type by a factor of 4, 22, and 3 respectively. 70 kDa FITC-dextran solute flux was similarly increased in elastase-treated carotids by a factor of 27. Solute uptake by Fbln5-/- carotids was decreased compared to wild-type for all investigated dextran sizes after 60 minutes of transmural transport. These changes in transport properties of elastic fiber compromised arteries have important implications for the kinetics of biomolecules and pharmaceuticals in arterial tissue following elastic fiber degradation due to aging or vascular disease.
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