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...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-02-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/5/2310 |
| _version_ | 1797395243786567680 |
|---|---|
| author | Amaia Garcia-Pena Jaime Ibarrola Adela Navarro Alba Sadaba Carolina Tiraplegui Mattie Garaikoetxea Vanessa Arrieta Lara Matilla Amaya Fernández-Celis Rafael Sadaba Virginia Alvarez Alicia Gainza Eva Jover Natalia López-Andrés |
| author_facet | Amaia Garcia-Pena Jaime Ibarrola Adela Navarro Alba Sadaba Carolina Tiraplegui Mattie Garaikoetxea Vanessa Arrieta Lara Matilla Amaya Fernández-Celis Rafael Sadaba Virginia Alvarez Alicia Gainza Eva Jover Natalia López-Andrés |
| author_sort | Amaia Garcia-Pena |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T00:31:37Z |
| format | Article |
| id | doaj.art-8f17dc587d114a42accba79e04fd8830 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:31:37Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8f17dc587d114a42accba79e04fd88302023-12-11T18:27:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01225231010.3390/ijms22052310Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve DiseaseAmaia Garcia-Pena0Jaime Ibarrola1Adela Navarro2Alba Sadaba3Carolina Tiraplegui4Mattie Garaikoetxea5Vanessa Arrieta6Lara Matilla7Amaya Fernández-Celis8Rafael Sadaba9Virginia Alvarez10Alicia Gainza11Eva Jover12Natalia López-Andrés13Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA. Irunlarrea 3, 31008 Pamplona, SpainMitral 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.https://www.mdpi.com/1422-0067/22/5/2310interleukin-33ST2mitral valvemyxomatousvalve endothelial cellsvalve interstitial cells |
| spellingShingle | Amaia Garcia-Pena Jaime Ibarrola Adela Navarro Alba Sadaba Carolina Tiraplegui Mattie Garaikoetxea Vanessa Arrieta Lara Matilla Amaya Fernández-Celis Rafael Sadaba Virginia Alvarez Alicia Gainza Eva Jover Natalia López-Andrés Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease International Journal of Molecular Sciences interleukin-33 ST2 mitral valve myxomatous valve endothelial cells valve interstitial cells |
| 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 | interleukin-33 ST2 mitral valve myxomatous valve endothelial cells valve interstitial cells |
| url | https://www.mdpi.com/1422-0067/22/5/2310 |
| work_keys_str_mv | AT amaiagarciapena activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT jaimeibarrola activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT adelanavarro activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT albasadaba activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT carolinatiraplegui activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT mattiegaraikoetxea activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT vanessaarrieta activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT laramatilla activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT amayafernandezcelis activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT rafaelsadaba activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT virginiaalvarez activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT aliciagainza activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT evajover activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease AT natalialopezandres activationoftheinterleukin33st2pathwayexertsdeleteriouseffectsinmyxomatousmitralvalvedisease |