Elastic Fiber Fragmentation Increases Transmural Hydraulic Conductance and Solute Transport in Mouse Arteries.

Abstract

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, noncontinuous 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 fluorescein isothiocyanate (FITC)-dextran were statistically increased in Fbln5-/- compared to wild-type by a factor of 4, 22, and 3, respectively. Similarly, elastase-treated carotids demonstrated a 27- and 13-fold increase in net solute flux of 70 and 150 kDa FITC-dextran, respectively, compared to untreated carotids, and 4 kDa FITC-dextran was unchanged between these groups. Solute uptake of 4 and 70 kDa FITC-dextran within Fbln5-/- carotids was decreased compared to wild-type for all investigated time points. 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.