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Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis

Calcific aortic valve disease (CAVD) is a highly prevalent and progressive disorder that ultimately causes gradual narrowing of the left ventricular outflow orifice with ensuing devastating hemodynamic effects on the heart. Calcific mineral accumulation is the hallmark pathology defining this proces...

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Autores principales: Büttner, Petra, Feistner, Lukas, Lurz, Philipp, Thiele, Holger, Hutcheson, Joshua D., Schlotter, Florian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143377/
https://www.ncbi.nlm.nih.gov/pubmed/34041283
http://dx.doi.org/10.3389/fcvm.2021.660797
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author Büttner, Petra
Feistner, Lukas
Lurz, Philipp
Thiele, Holger
Hutcheson, Joshua D.
Schlotter, Florian
author_facet Büttner, Petra
Feistner, Lukas
Lurz, Philipp
Thiele, Holger
Hutcheson, Joshua D.
Schlotter, Florian
author_sort Büttner, Petra
collection PubMed
description Calcific aortic valve disease (CAVD) is a highly prevalent and progressive disorder that ultimately causes gradual narrowing of the left ventricular outflow orifice with ensuing devastating hemodynamic effects on the heart. Calcific mineral accumulation is the hallmark pathology defining this process; however, fibrotic extracellular matrix (ECM) remodeling that leads to extensive deposition of fibrous connective tissue and distortion of the valvular microarchitecture similarly has major biomechanical and functional consequences for heart valve function. Significant advances have been made to unravel the complex mechanisms that govern these active, cell-mediated processes, yet the interplay between fibrosis and calcification and the individual contribution to progressive extracellular matrix stiffening require further clarification. Specifically, we discuss (1) the valvular biomechanics and layered ECM composition, (2) patterns in the cellular contribution, temporal onset, and risk factors for valvular fibrosis, (3) imaging valvular fibrosis, (4) biomechanical implications of valvular fibrosis, and (5) molecular mechanisms promoting fibrotic tissue remodeling and the possibility of reverse remodeling. This review explores our current understanding of the cellular and molecular drivers of fibrogenesis and the pathophysiological role of fibrosis in CAVD.
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spelling pubmed-81433772021-05-25 Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis Büttner, Petra Feistner, Lukas Lurz, Philipp Thiele, Holger Hutcheson, Joshua D. Schlotter, Florian Front Cardiovasc Med Cardiovascular Medicine Calcific aortic valve disease (CAVD) is a highly prevalent and progressive disorder that ultimately causes gradual narrowing of the left ventricular outflow orifice with ensuing devastating hemodynamic effects on the heart. Calcific mineral accumulation is the hallmark pathology defining this process; however, fibrotic extracellular matrix (ECM) remodeling that leads to extensive deposition of fibrous connective tissue and distortion of the valvular microarchitecture similarly has major biomechanical and functional consequences for heart valve function. Significant advances have been made to unravel the complex mechanisms that govern these active, cell-mediated processes, yet the interplay between fibrosis and calcification and the individual contribution to progressive extracellular matrix stiffening require further clarification. Specifically, we discuss (1) the valvular biomechanics and layered ECM composition, (2) patterns in the cellular contribution, temporal onset, and risk factors for valvular fibrosis, (3) imaging valvular fibrosis, (4) biomechanical implications of valvular fibrosis, and (5) molecular mechanisms promoting fibrotic tissue remodeling and the possibility of reverse remodeling. This review explores our current understanding of the cellular and molecular drivers of fibrogenesis and the pathophysiological role of fibrosis in CAVD. Frontiers Media S.A. 2021-05-10 /pmc/articles/PMC8143377/ /pubmed/34041283 http://dx.doi.org/10.3389/fcvm.2021.660797 Text en Copyright © 2021 Büttner, Feistner, Lurz, Thiele, Hutcheson and Schlotter. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Büttner, Petra
Feistner, Lukas
Lurz, Philipp
Thiele, Holger
Hutcheson, Joshua D.
Schlotter, Florian
Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis
title Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis
title_full Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis
title_fullStr Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis
title_full_unstemmed Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis
title_short Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis
title_sort dissecting calcific aortic valve disease—the role, etiology, and drivers of valvular fibrosis
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143377/
https://www.ncbi.nlm.nih.gov/pubmed/34041283
http://dx.doi.org/10.3389/fcvm.2021.660797
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