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Correlation of Micro-Computed Tomography Assessment of Valvular Mineralisation with Histopathological and Immunohistochemical Features of Calcific Aortic Valve Disease

Aortic valve stenosis is a serious disease with increasing prevalence in developed countries. Research aimed at uncovering the molecular mechanisms behind its main cause, aortic valve calcification, is thus crucial for the development of future therapies. It is frequently difficult to measure the ex...

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Autores principales: Solache-Berrocal, Guillermo, Barral-Varela, Ana María, Areces-Rodríguez, Sheila, Junco-Vicente, Alejandro, Vallina-Álvarez, Aitana, Corte-Torres, María Daniela, Valdivielso, José Manuel, Llosa, Juan Carlos, Morís, César, Martín, María, Rodríguez, Isabel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019701/
https://www.ncbi.nlm.nih.gov/pubmed/31877754
http://dx.doi.org/10.3390/jcm9010029
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author Solache-Berrocal, Guillermo
Barral-Varela, Ana María
Areces-Rodríguez, Sheila
Junco-Vicente, Alejandro
Vallina-Álvarez, Aitana
Corte-Torres, María Daniela
Valdivielso, José Manuel
Llosa, Juan Carlos
Morís, César
Martín, María
Rodríguez, Isabel
author_facet Solache-Berrocal, Guillermo
Barral-Varela, Ana María
Areces-Rodríguez, Sheila
Junco-Vicente, Alejandro
Vallina-Álvarez, Aitana
Corte-Torres, María Daniela
Valdivielso, José Manuel
Llosa, Juan Carlos
Morís, César
Martín, María
Rodríguez, Isabel
author_sort Solache-Berrocal, Guillermo
collection PubMed
description Aortic valve stenosis is a serious disease with increasing prevalence in developed countries. Research aimed at uncovering the molecular mechanisms behind its main cause, aortic valve calcification, is thus crucial for the development of future therapies. It is frequently difficult to measure the extent of mineralisation in soft tissues and some methods require the destruction of the sample. Micro-computed tomography (µCT), a non-destructive technique, was used to quantify the density and volume of calcium deposits on cusps from 57 explanted aortic valves. Conventional and immunostaining techniques were used to characterise valve tissue degeneration and the inflammatory and osteogenic stage with several markers. Although most of the analysed cusps came from severe stenosis patients, the µCT parameter bone volume/tissue volume ratio distinguished several degrees of mineralisation that correlated with the degree of structural change in the tissue and the amount of macrophage infiltration as determined by CD68 immunohistochemistry. Interestingly, exosomal markers CD63 and Alix co-localised with macrophage infiltration surrounding calcium deposits, suggesting that those vesicles could be produced at least in part by these immune cells. In conclusion, we have shown that the ex vivo assessment of aortic valve mineralisation with µCT reflects the molecular and cellular changes in pathological valves during progression towards stenosis. Thus, our results give additional validity to quantitative μCT as a convenient laboratory tool for basic research on this type of cardiovascular calcification.
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spelling pubmed-70197012020-03-09 Correlation of Micro-Computed Tomography Assessment of Valvular Mineralisation with Histopathological and Immunohistochemical Features of Calcific Aortic Valve Disease Solache-Berrocal, Guillermo Barral-Varela, Ana María Areces-Rodríguez, Sheila Junco-Vicente, Alejandro Vallina-Álvarez, Aitana Corte-Torres, María Daniela Valdivielso, José Manuel Llosa, Juan Carlos Morís, César Martín, María Rodríguez, Isabel J Clin Med Article Aortic valve stenosis is a serious disease with increasing prevalence in developed countries. Research aimed at uncovering the molecular mechanisms behind its main cause, aortic valve calcification, is thus crucial for the development of future therapies. It is frequently difficult to measure the extent of mineralisation in soft tissues and some methods require the destruction of the sample. Micro-computed tomography (µCT), a non-destructive technique, was used to quantify the density and volume of calcium deposits on cusps from 57 explanted aortic valves. Conventional and immunostaining techniques were used to characterise valve tissue degeneration and the inflammatory and osteogenic stage with several markers. Although most of the analysed cusps came from severe stenosis patients, the µCT parameter bone volume/tissue volume ratio distinguished several degrees of mineralisation that correlated with the degree of structural change in the tissue and the amount of macrophage infiltration as determined by CD68 immunohistochemistry. Interestingly, exosomal markers CD63 and Alix co-localised with macrophage infiltration surrounding calcium deposits, suggesting that those vesicles could be produced at least in part by these immune cells. In conclusion, we have shown that the ex vivo assessment of aortic valve mineralisation with µCT reflects the molecular and cellular changes in pathological valves during progression towards stenosis. Thus, our results give additional validity to quantitative μCT as a convenient laboratory tool for basic research on this type of cardiovascular calcification. MDPI 2019-12-21 /pmc/articles/PMC7019701/ /pubmed/31877754 http://dx.doi.org/10.3390/jcm9010029 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Solache-Berrocal, Guillermo
Barral-Varela, Ana María
Areces-Rodríguez, Sheila
Junco-Vicente, Alejandro
Vallina-Álvarez, Aitana
Corte-Torres, María Daniela
Valdivielso, José Manuel
Llosa, Juan Carlos
Morís, César
Martín, María
Rodríguez, Isabel
Correlation of Micro-Computed Tomography Assessment of Valvular Mineralisation with Histopathological and Immunohistochemical Features of Calcific Aortic Valve Disease
title Correlation of Micro-Computed Tomography Assessment of Valvular Mineralisation with Histopathological and Immunohistochemical Features of Calcific Aortic Valve Disease
title_full Correlation of Micro-Computed Tomography Assessment of Valvular Mineralisation with Histopathological and Immunohistochemical Features of Calcific Aortic Valve Disease
title_fullStr Correlation of Micro-Computed Tomography Assessment of Valvular Mineralisation with Histopathological and Immunohistochemical Features of Calcific Aortic Valve Disease
title_full_unstemmed Correlation of Micro-Computed Tomography Assessment of Valvular Mineralisation with Histopathological and Immunohistochemical Features of Calcific Aortic Valve Disease
title_short Correlation of Micro-Computed Tomography Assessment of Valvular Mineralisation with Histopathological and Immunohistochemical Features of Calcific Aortic Valve Disease
title_sort correlation of micro-computed tomography assessment of valvular mineralisation with histopathological and immunohistochemical features of calcific aortic valve disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019701/
https://www.ncbi.nlm.nih.gov/pubmed/31877754
http://dx.doi.org/10.3390/jcm9010029
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