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Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease
Mitral valve disease (MVD) is a frequent cause of heart failure and death worldwide, but its etiopathogenesis is not fully understood. Interleukin (IL)-33 regulates inflammation and thrombosis in the vascular endothelium and may play a role in the atherosclerotic process, but its role in mitral valv...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956196/ https://www.ncbi.nlm.nih.gov/pubmed/33669101 http://dx.doi.org/10.3390/ijms22052310 |
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author | Garcia-Pena, Amaia Ibarrola, Jaime Navarro, Adela Sadaba, Alba Tiraplegui, Carolina Garaikoetxea, Mattie Arrieta, Vanessa Matilla, Lara Fernández-Celis, Amaya Sadaba, Rafael Alvarez, Virginia Gainza, Alicia Jover, Eva López-Andrés, Natalia |
author_facet | Garcia-Pena, Amaia Ibarrola, Jaime Navarro, Adela Sadaba, Alba Tiraplegui, Carolina Garaikoetxea, Mattie Arrieta, Vanessa Matilla, Lara Fernández-Celis, Amaya Sadaba, Rafael Alvarez, Virginia Gainza, Alicia Jover, Eva López-Andrés, Natalia |
author_sort | Garcia-Pena, Amaia |
collection | PubMed |
description | Mitral valve disease (MVD) is a frequent cause of heart failure and death worldwide, but its etiopathogenesis is not fully understood. Interleukin (IL)-33 regulates inflammation and thrombosis in the vascular endothelium and may play a role in the atherosclerotic process, but its role in mitral valve has not been investigated. We aim to explore IL-33 as a possible inductor of myxomatous degeneration in human mitral valves. We enrolled 103 patients suffering from severe mitral regurgitation due to myxomatous degeneration undergoing mitral valve replacement. Immunohistochemistry of the resected leaflets showed IL-33 and ST2 expression in both valve interstitial cells (VICs) and valve endothelial cells (VECs). Positive correlations were found between the levels of IL-33 and molecules implicated in the development of myxomatous MVD, such as proteoglycans, extracellular matrix remodeling enzymes (matrix metalloproteinases and their tissue inhibitors), inflammatory and fibrotic markers. Stimulation of single cell cultures of VICs and VECs with recombinant human IL-33 induced the expression of activated VIC markers, endothelial–mesenchymal transition of VECs, proteoglycan synthesis, inflammatory molecules and extracellular matrix turnover. Our findings suggest that the IL-33/ST2 system may be involved in the development of myxomatous MVD by enhancing extracellular matrix remodeling. |
format | Online Article Text |
id | pubmed-7956196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79561962021-03-15 Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease Garcia-Pena, Amaia Ibarrola, Jaime Navarro, Adela Sadaba, Alba Tiraplegui, Carolina Garaikoetxea, Mattie Arrieta, Vanessa Matilla, Lara Fernández-Celis, Amaya Sadaba, Rafael Alvarez, Virginia Gainza, Alicia Jover, Eva López-Andrés, Natalia Int J Mol Sci Article Mitral valve disease (MVD) is a frequent cause of heart failure and death worldwide, but its etiopathogenesis is not fully understood. Interleukin (IL)-33 regulates inflammation and thrombosis in the vascular endothelium and may play a role in the atherosclerotic process, but its role in mitral valve has not been investigated. We aim to explore IL-33 as a possible inductor of myxomatous degeneration in human mitral valves. We enrolled 103 patients suffering from severe mitral regurgitation due to myxomatous degeneration undergoing mitral valve replacement. Immunohistochemistry of the resected leaflets showed IL-33 and ST2 expression in both valve interstitial cells (VICs) and valve endothelial cells (VECs). Positive correlations were found between the levels of IL-33 and molecules implicated in the development of myxomatous MVD, such as proteoglycans, extracellular matrix remodeling enzymes (matrix metalloproteinases and their tissue inhibitors), inflammatory and fibrotic markers. Stimulation of single cell cultures of VICs and VECs with recombinant human IL-33 induced the expression of activated VIC markers, endothelial–mesenchymal transition of VECs, proteoglycan synthesis, inflammatory molecules and extracellular matrix turnover. Our findings suggest that the IL-33/ST2 system may be involved in the development of myxomatous MVD by enhancing extracellular matrix remodeling. MDPI 2021-02-25 /pmc/articles/PMC7956196/ /pubmed/33669101 http://dx.doi.org/10.3390/ijms22052310 Text en © 2021 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 Garcia-Pena, Amaia Ibarrola, Jaime Navarro, Adela Sadaba, Alba Tiraplegui, Carolina Garaikoetxea, Mattie Arrieta, Vanessa Matilla, Lara Fernández-Celis, Amaya Sadaba, Rafael Alvarez, Virginia Gainza, Alicia Jover, Eva López-Andrés, Natalia Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease |
title | Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease |
title_full | Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease |
title_fullStr | Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease |
title_full_unstemmed | Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease |
title_short | Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease |
title_sort | activation of the interleukin-33/st2 pathway exerts deleterious effects in myxomatous mitral valve disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956196/ https://www.ncbi.nlm.nih.gov/pubmed/33669101 http://dx.doi.org/10.3390/ijms22052310 |
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