TY - JOUR
T1 - Elastic fiber fragmentation increases transmural hydraulic conductance and solute transport in mouse arteries
AU - Cocciolone, Austin J.
AU - Johnson, Elizabeth O.
AU - Shao, Jin Yu
AU - Wagenseil, Jessica E.
N1 - Funding Information:
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (Grant No. P30AR057235, Funder ID. 10.13039/ 100000069).
Funding Information:
• National Institute of Biomedical Imaging and Bioengineering (Grant No. T32EB018266, Funder ID. 10.13039/100000070).
Funding Information:
Hiromi Yanagisawa at the University of Tsukuba is gratefully acknowledged for providing the Fbln5−/− mice. Data presented in this study were partially funded by NIH grants R01HL115560, R01HL105314, and T32EB018266. Histological data were partially provided by the Washington University Musculoskeletal Research Center funded by NIH grant P30 AR057235. Confocal data were generated on a Zeiss LSM 880 Airyscan Confocal Microscope which was purchased with support from the Office of Research Infrastructure Programs (ORIP), a part of the NIH Office of the Director under grant OD021629. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Funding Information:
• NIH Office of the Director (Grant No. OD021629, Funder ID. 10.13039/100000052).
Publisher Copyright:
Copyright © 2019 by ASME.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
KW - elastic fiber matrix
KW - fibulin-5
KW - porous membrane
UR - http://www.scopus.com/inward/record.url?scp=85058957468&partnerID=8YFLogxK
U2 - 10.1115/1.4042173
DO - 10.1115/1.4042173
M3 - Article
C2 - 30516242
AN - SCOPUS:85058957468
SN - 0148-0731
VL - 141
JO - Journal of Biomechanical Engineering
JF - Journal of Biomechanical Engineering
IS - 2
M1 - 021013
ER -