Cargando…

Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart

Intracardiac haemodynamics is crucial for normal cardiogenesis, with recent evidence showing valvulogenesis is haemodynamically dependent and inextricably linked with shear stress. Although valve anomalies have been associated with genetic mutations, often the cause is unknown. However, altered haem...

Descripción completa

Detalles Bibliográficos
Autores principales: Pang, Kar Lai, Parnall, Matthew, Loughna, Siobhan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Academic Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529288/
https://www.ncbi.nlm.nih.gov/pubmed/28576718
http://dx.doi.org/10.1016/j.yjmcc.2017.05.012
_version_ 1783253089348747264
author Pang, Kar Lai
Parnall, Matthew
Loughna, Siobhan
author_facet Pang, Kar Lai
Parnall, Matthew
Loughna, Siobhan
author_sort Pang, Kar Lai
collection PubMed
description Intracardiac haemodynamics is crucial for normal cardiogenesis, with recent evidence showing valvulogenesis is haemodynamically dependent and inextricably linked with shear stress. Although valve anomalies have been associated with genetic mutations, often the cause is unknown. However, altered haemodynamics have been suggested as a pathogenic contributor to bicuspid aortic valve disease. Conversely, how abnormal haemodynamics impacts mitral valve development is still poorly understood. In order to analyse altered blood flow, the outflow tract of the chick heart was constricted using a ligature to increase cardiac pressure overload. Outflow tract-banding was performed at HH21, with harvesting at crucial valve development stages (HH26, HH29 and HH35). Although normal valve morphology was found in HH26 outflow tract banded hearts, smaller and dysmorphic mitral valve primordia were seen upon altered haemodynamics in histological and stereological analysis at HH29 and HH35. A decrease in apoptosis, and aberrant expression of a shear stress responsive gene and extracellular matrix markers in the endocardial cushions were seen in the chick HH29 outflow tract banded hearts. In addition, dysregulation of extracellular matrix (ECM) proteins fibrillin-2, type III collagen and tenascin were further demonstrated in more mature primordial mitral valve leaflets at HH35, with a concomitant decrease of ECM cross-linking enzyme, transglutaminase-2. These data provide compelling evidence that normal haemodynamics are a prerequisite for normal mitral valve morphogenesis, and abnormal blood flow could be a contributing factor in mitral valve defects, with differentiation as a possible underlying mechanism.
format Online
Article
Text
id pubmed-5529288
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Academic Press
record_format MEDLINE/PubMed
spelling pubmed-55292882017-07-31 Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart Pang, Kar Lai Parnall, Matthew Loughna, Siobhan J Mol Cell Cardiol Article Intracardiac haemodynamics is crucial for normal cardiogenesis, with recent evidence showing valvulogenesis is haemodynamically dependent and inextricably linked with shear stress. Although valve anomalies have been associated with genetic mutations, often the cause is unknown. However, altered haemodynamics have been suggested as a pathogenic contributor to bicuspid aortic valve disease. Conversely, how abnormal haemodynamics impacts mitral valve development is still poorly understood. In order to analyse altered blood flow, the outflow tract of the chick heart was constricted using a ligature to increase cardiac pressure overload. Outflow tract-banding was performed at HH21, with harvesting at crucial valve development stages (HH26, HH29 and HH35). Although normal valve morphology was found in HH26 outflow tract banded hearts, smaller and dysmorphic mitral valve primordia were seen upon altered haemodynamics in histological and stereological analysis at HH29 and HH35. A decrease in apoptosis, and aberrant expression of a shear stress responsive gene and extracellular matrix markers in the endocardial cushions were seen in the chick HH29 outflow tract banded hearts. In addition, dysregulation of extracellular matrix (ECM) proteins fibrillin-2, type III collagen and tenascin were further demonstrated in more mature primordial mitral valve leaflets at HH35, with a concomitant decrease of ECM cross-linking enzyme, transglutaminase-2. These data provide compelling evidence that normal haemodynamics are a prerequisite for normal mitral valve morphogenesis, and abnormal blood flow could be a contributing factor in mitral valve defects, with differentiation as a possible underlying mechanism. Academic Press 2017-07 /pmc/articles/PMC5529288/ /pubmed/28576718 http://dx.doi.org/10.1016/j.yjmcc.2017.05.012 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pang, Kar Lai
Parnall, Matthew
Loughna, Siobhan
Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart
title Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart
title_full Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart
title_fullStr Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart
title_full_unstemmed Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart
title_short Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart
title_sort effect of altered haemodynamics on the developing mitral valve in chick embryonic heart
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529288/
https://www.ncbi.nlm.nih.gov/pubmed/28576718
http://dx.doi.org/10.1016/j.yjmcc.2017.05.012
work_keys_str_mv AT pangkarlai effectofalteredhaemodynamicsonthedevelopingmitralvalveinchickembryonicheart
AT parnallmatthew effectofalteredhaemodynamicsonthedevelopingmitralvalveinchickembryonicheart
AT loughnasiobhan effectofalteredhaemodynamicsonthedevelopingmitralvalveinchickembryonicheart