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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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