Faculty Collaboration Database

Altered hemodynamics, endothelial function, and protein expression occur with aortic coarctation and persist after repair. Am J Physiol Heart Circ Physiol 2012 Dec 01;303(11):H1304-18

Date

10/02/2012

Pubmed ID

23023871

Pubmed Central ID

PMC3532538

DOI

10.1152/ajpheart.00420.2012

Scopus ID

2-s2.0-84870510439 (requires institutional sign-in at Scopus site)   37 Citations

Abstract

Coarctation of the aorta (CoA) is associated with substantial morbidity despite treatment. Mechanically induced structural and functional vascular changes are implicated; however, their relationship with smooth muscle (SM) phenotypic expression is not fully understood. Using a clinically representative rabbit model of CoA and correction, we quantified mechanical alterations from a 20-mmHg blood pressure (BP) gradient in the thoracic aorta and related the expression of key SM contractile and focal adhesion proteins with remodeling, relaxation, and stiffness. Systolic and mean BP were elevated for CoA rabbits compared with controls leading to remodeling, stiffening, an altered force response, and endothelial dysfunction both proximally and distally. The proximal changes persisted for corrected rabbits despite >12 wk of normal BP (~4 human years). Computational fluid dynamic simulations revealed reduced wall shear stress (WSS) proximally in CoA compared with control and corrected rabbits. Distally, WSS was markedly increased in CoA rabbits due to a stenotic velocity jet, which has persistent effects as WSS was significantly reduced in corrected rabbits. Immunohistochemistry revealed significantly increased nonmuscle myosin and reduced SM myosin heavy chain expression in the proximal arteries of CoA and corrected rabbits but no differences in SM α-actin, talin, or fibronectin. These findings indicate that CoA can cause alterations in the SM phenotype contributing to structural and functional changes in the proximal arteries that accompany the mechanical stimuli of elevated BP and altered WSS. Importantly, these changes are not reversed upon BP correction and may serve as markers of disease severity, which explains the persistent morbidity observed in CoA patients.

Author List

Menon A, Eddinger TJ, Wang H, Wendell DC, Toth JM, LaDisa JF Jr

Authors

Thomas Eddinger PhD Bioological Sciences in the Biology department at Marquette University
John F. LaDisa PhD Professor in the Pediatrics department at Medical College of Wisconsin
Jeffrey M. Toth PhD Associate Dean for Research in the School of Dentistry department at Marquette University

MESH terms used to index this publication - Major topics in bold

Actins
Animals
Aortic Coarctation
Blood Pressure
Cardiovascular Surgical Procedures
Contractile Proteins
Endothelium, Vascular
Fibronectins
Hemodynamics
Male
Models, Animal
Myosin Heavy Chains
Rabbits
Shear Strength
Stress, Mechanical
Talin