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Development and maturation of the fibrous components of the arterial roots in the mouse heart

Lookup NU author(s): Dr Rachel Richardson, Dr Lorraine Eley, Charlotte Donald-Wilson, Natasha Curley, Ahlam Alqahtani, Dr Lindsay Murphy, Professor Robert Anderson, Professor Deborah Henderson, Dr Bill Chaudhry

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

The arterial roots are important transitional regions of the heart, connecting the intrapericardial componentsof the aortic and pulmonary trunks with their ventricular outlets. They house the arterial (semilunar) valvesand, in the case of the aorta, are the points of coronary arterial attachment. Moreover, because of thesemilunar attachments of the valve leaflets, the arterial roots span the anatomic ventriculo-arterial junction. Byvirtue of this arrangement, the interleaflet triangles, despite being fibrous, are found on the ventricular aspectof the root and located within the left ventricular cavity. Malformations and diseases of the aortic root arecommon and serious. Despite the mouse being the animal model of choice for studying cardiac development,few studies have examined the structure of their arterial roots. As a consequence, our understanding of theirformation and maturation is incomplete. We set out to clarify the anatomical and histological features of themouse arterial roots, particularly focusing on their walls and the points of attachment of the valve leaflets. Wethen sought to determine the embryonic lineage relationships between these tissues, as a forerunner tounderstanding how they form and mature over time. Using histological stains and immunohistochemistry, weshow that the walls of the mouse arterial roots show a gradual transition, with smooth muscle cells (SMC)forming the bulk of wall at the most distal points of attachments of the valve leaflets, while being entirelyfibrous at their base. Although the interleaflet triangles lie within the ventricular chambers, we show that theyare histologically indistinguishable from the arterial sinus walls until the end of gestation. Differences becomeapparent after birth, and are only completed by postnatal day 21. Using Cre-lox-based lineage tracingtechnology to label progenitor populations, we show that the SMC and fibrous tissue within the walls of themature arterial roots share a common origin from the second heart field (SHF) and exclude trans-differentiationof myocardium as a source for the interleaflet triangle fibrous tissues. Moreover, we show that the attachmentpoints of the leaflets to the walls, like the leaflets themselves, are derived from the outflow cushions, havingcontributions from both SHF-derived endothelial cells and neural crest cells. Our data thus show that the5 arterial roots in the mouse heart are similar to the features described in human heart. They provide aframework for understanding complex lesions and diseases affecting the aortic root.


Publication metadata

Author(s): Richardson R, Eley L, Donald-Wilson C, Davis J, Curley N, Alqahtani A, Murphy L, Anderson RH, Henderson DJ, Chaudhry B

Publication type: Article

Publication status: Published

Journal: Journal of Anatomy

Year: 2018

Volume: 232

Issue: 4

Pages: 554-567

Print publication date: 01/04/2018

Online publication date: 15/10/2017

Acceptance date: 30/08/2017

Date deposited: 13/10/2017

ISSN (print): 0021-8782

ISSN (electronic): 1469-7580

Publisher: Wiley

URL: https://doi.org/10.1111/joa.12713

DOI: 10.1111/joa.12713

PubMed id: 29034473


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