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Aortic Remodeling Kinetics in Response to Coarctation-Induced Mechanical Perturbations. Biomedicines 2023 Jun 25;11(7)

Date

07/29/2023

Pubmed ID

37509457

Pubmed Central ID

PMC10377168

DOI

10.3390/biomedicines11071817

Scopus ID

2-s2.0-85175103038 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

Background: Coarctation of the aorta (CoA; constriction of the proximal descending thoracic aorta) is among the most common congenital cardiovascular defects. Coarctation-induced mechanical perturbations trigger a cycle of mechano-transduction events leading to irreversible precursors of hypertension including arterial thickening, stiffening, and vasoactive dysfunction in proximal conduit arteries. This study sought to identify kinetics of the stress-mediated compensatory response leading to these alterations using a preclinical rabbit model of CoA. Methods: A prior growth and remodeling (G&R) framework was reformulated and fit to empirical measurements from CoA rabbits classified into one control and nine CoA groups of various severities and durations (n = 63, 5-11/group). Empirical measurements included Doppler ultrasound imaging, uniaxial extension testing, catheter-based blood pressure, and wire myography, yielding the time evolution of arterial thickening, stiffening, and vasoactive dysfunction required to fit G&R constitutive parameters. Results: Excellent agreement was observed between model predictions and observed patterns of arterial thickening, stiffening, and dysfunction among all CoA groups. For example, predicted vascular impairment was not significantly different from empirical observations via wire myography (p-value > 0.13). Specifically, 48% and 45% impairment was observed in smooth muscle contraction and endothelial-dependent relaxation, respectively, which were accurately predicted using the G&R model. Conclusions: The resulting G&R model, for the first time, allows for prediction of hypertension precursors at neonatal ages that is currently challenging to examine in preclinical models. These findings provide a validated computational tool for prediction of persistent arterial dysfunction and identification of revised severity-duration thresholds that may ultimately avoid hypertension from CoA.

Author List

Ghorbannia A, Maadooliat M, Woods RK, Audi SH, Tefft BJ, Chiastra C, Ibrahim ESH, LaDisa JF

Authors

Said Audi PhD Professor in the Biomedical Engineering department at Marquette University
John F. LaDisa PhD Professor in the Pediatrics department at Medical College of Wisconsin
Brandon J. Tefft PhD Assistant Professor in the Biomedical Engineering department at Medical College of Wisconsin
Ronald K. Woods MD Professor in the Surgery department at Medical College of Wisconsin