Cargando…

The Genetic Regulation of Aortic Valve Development and Calcific Disease

Heart valves are dynamic, highly organized structures required for unidirectional blood flow through the heart. Over an average lifetime, the valve leaflets or cusps open and close over a billion times, however in over 5 million Americans, leaflet function fails due to biomechanical insufficiency in...

Descripción completa

Detalles Bibliográficos
Autores principales: Menon, Vinal, Lincoln, Joy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232166/
https://www.ncbi.nlm.nih.gov/pubmed/30460247
http://dx.doi.org/10.3389/fcvm.2018.00162
_version_ 1783370355782451200
author Menon, Vinal
Lincoln, Joy
author_facet Menon, Vinal
Lincoln, Joy
author_sort Menon, Vinal
collection PubMed
description Heart valves are dynamic, highly organized structures required for unidirectional blood flow through the heart. Over an average lifetime, the valve leaflets or cusps open and close over a billion times, however in over 5 million Americans, leaflet function fails due to biomechanical insufficiency in response to wear-and-tear or pathological stimulus. Calcific aortic valve disease (CAVD) is the most common valve pathology and leads to stiffening of the cusp and narrowing of the aortic orifice leading to stenosis and insufficiency. At the cellular level, CAVD is characterized by valve endothelial cell dysfunction and osteoblast-like differentiation of valve interstitial cells. These processes are associated with dysregulation of several molecular pathways important for valve development including Notch, Sox9, Tgfβ, Bmp, Wnt, as well as additional epigenetic regulators. In this review, we discuss the multifactorial mechanisms that contribute to CAVD pathogenesis and the potential of targeting these for the development of novel, alternative therapeutics beyond surgical intervention.
format Online
Article
Text
id pubmed-6232166
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-62321662018-11-20 The Genetic Regulation of Aortic Valve Development and Calcific Disease Menon, Vinal Lincoln, Joy Front Cardiovasc Med Cardiovascular Medicine Heart valves are dynamic, highly organized structures required for unidirectional blood flow through the heart. Over an average lifetime, the valve leaflets or cusps open and close over a billion times, however in over 5 million Americans, leaflet function fails due to biomechanical insufficiency in response to wear-and-tear or pathological stimulus. Calcific aortic valve disease (CAVD) is the most common valve pathology and leads to stiffening of the cusp and narrowing of the aortic orifice leading to stenosis and insufficiency. At the cellular level, CAVD is characterized by valve endothelial cell dysfunction and osteoblast-like differentiation of valve interstitial cells. These processes are associated with dysregulation of several molecular pathways important for valve development including Notch, Sox9, Tgfβ, Bmp, Wnt, as well as additional epigenetic regulators. In this review, we discuss the multifactorial mechanisms that contribute to CAVD pathogenesis and the potential of targeting these for the development of novel, alternative therapeutics beyond surgical intervention. Frontiers Media S.A. 2018-11-06 /pmc/articles/PMC6232166/ /pubmed/30460247 http://dx.doi.org/10.3389/fcvm.2018.00162 Text en Copyright © 2018 Menon and Lincoln. http://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
Menon, Vinal
Lincoln, Joy
The Genetic Regulation of Aortic Valve Development and Calcific Disease
title The Genetic Regulation of Aortic Valve Development and Calcific Disease
title_full The Genetic Regulation of Aortic Valve Development and Calcific Disease
title_fullStr The Genetic Regulation of Aortic Valve Development and Calcific Disease
title_full_unstemmed The Genetic Regulation of Aortic Valve Development and Calcific Disease
title_short The Genetic Regulation of Aortic Valve Development and Calcific Disease
title_sort genetic regulation of aortic valve development and calcific disease
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232166/
https://www.ncbi.nlm.nih.gov/pubmed/30460247
http://dx.doi.org/10.3389/fcvm.2018.00162
work_keys_str_mv AT menonvinal thegeneticregulationofaorticvalvedevelopmentandcalcificdisease
AT lincolnjoy thegeneticregulationofaorticvalvedevelopmentandcalcificdisease
AT menonvinal geneticregulationofaorticvalvedevelopmentandcalcificdisease
AT lincolnjoy geneticregulationofaorticvalvedevelopmentandcalcificdisease