Role for Galectin‐3 in Calcific Aortic Valve Stenosis
BackgroundAortic stenosis (AS) is a chronic inflammatory disease, and calcification plays an important role in the progression of the disease. Galectin‐3 (Gal‐3) is a proinflammatory molecule involved in vascular osteogenesis in atherosclerosis. Therefore, we hypothesized that Gal‐3 could mediate va...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-10-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.116.004360 |
| _version_ | 1831523004843032576 |
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| author | J. Rafael Sádaba Ernesto Martínez‐Martínez Vanessa Arrieta Virginia Álvarez Amaya Fernández‐Celis Jaime Ibarrola Amaia Melero Patrick Rossignol Victoria Cachofeiro Natalia López‐Andrés |
| author_facet | J. Rafael Sádaba Ernesto Martínez‐Martínez Vanessa Arrieta Virginia Álvarez Amaya Fernández‐Celis Jaime Ibarrola Amaia Melero Patrick Rossignol Victoria Cachofeiro Natalia López‐Andrés |
| author_sort | J. Rafael Sádaba |
| collection | DOAJ |
| description | BackgroundAortic stenosis (AS) is a chronic inflammatory disease, and calcification plays an important role in the progression of the disease. Galectin‐3 (Gal‐3) is a proinflammatory molecule involved in vascular osteogenesis in atherosclerosis. Therefore, we hypothesized that Gal‐3 could mediate valve calcification in AS. Methods and ResultsBlood samples and aortic valves (AVs) from 77 patients undergoing AV replacement were analyzed. As controls, noncalcified human AVs were obtained at autopsy (n=11). Gal‐3 was spontaneously expressed in valvular interstitial cells (VICs) from AVs and increased in AS as compared to control AVs. Positive correlations were found between circulating and valvular Gal‐3 levels. Valvular Gal‐3 colocalized with the VICs markers, alpha‐smooth muscle actin and vimentin, and with the osteogenic markers, osteopontin, bone morphogenetic protein 2, runt‐related transcription factor 2, and SRY (sex‐determining region Y)‐box 9. Gal‐3 also colocalized with the inflammatory markers cd68, cd80 and tumor necrosis factor alpha. In vitro, in VICs isolated from AVs, Gal‐3 induced expression of inflammatory, fibrotic, and osteogenic markers through the extracellular signal‐regulated kinase 1 and 2 pathway. Gal‐3 expression was blocked in VICs undergoing osteoblastic differentiation using its pharmacological inhibitor, modified citrus pectin, or the clustered regularly interspaced short palindromic repeats/Cas9 knockout system. Gal‐3 blockade and knockdown decreased the expression of inflammatory, fibrotic, and osteogenic markers in differentiated VICs. ConclusionsGal‐3, which is overexpressed in AVs from AS patients, appears to play a central role in calcification in AS. Gal‐3 could be a new therapeutic approach to delay the progression of AV calcification in AS. |
| first_indexed | 2024-12-14T07:08:40Z |
| format | Article |
| id | doaj.art-f6fd0bede13e42d1a45d340abc967e93 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-14T07:08:40Z |
| publishDate | 2016-10-01 |
| publisher | Wiley |
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| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-f6fd0bede13e42d1a45d340abc967e932022-12-21T23:12:04ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-10-0151110.1161/JAHA.116.004360Role for Galectin‐3 in Calcific Aortic Valve StenosisJ. Rafael Sádaba0Ernesto Martínez‐Martínez1Vanessa Arrieta2Virginia Álvarez3Amaya Fernández‐Celis4Jaime Ibarrola5Amaia Melero6Patrick Rossignol7Victoria Cachofeiro8Natalia López‐Andrés9Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainINSERM, Centre d'Investigations Cliniques‐Plurithématique 1433, UMR 1116, CHRU de Nancy, Université de Lorraine French‐Clinical Research Infrastructure Network (F‐CRIN) INI‐CRCT, Nancy, FranceDepartment of Physiology, School of Medicine, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense, Madrid, SpainCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainBackgroundAortic stenosis (AS) is a chronic inflammatory disease, and calcification plays an important role in the progression of the disease. Galectin‐3 (Gal‐3) is a proinflammatory molecule involved in vascular osteogenesis in atherosclerosis. Therefore, we hypothesized that Gal‐3 could mediate valve calcification in AS. Methods and ResultsBlood samples and aortic valves (AVs) from 77 patients undergoing AV replacement were analyzed. As controls, noncalcified human AVs were obtained at autopsy (n=11). Gal‐3 was spontaneously expressed in valvular interstitial cells (VICs) from AVs and increased in AS as compared to control AVs. Positive correlations were found between circulating and valvular Gal‐3 levels. Valvular Gal‐3 colocalized with the VICs markers, alpha‐smooth muscle actin and vimentin, and with the osteogenic markers, osteopontin, bone morphogenetic protein 2, runt‐related transcription factor 2, and SRY (sex‐determining region Y)‐box 9. Gal‐3 also colocalized with the inflammatory markers cd68, cd80 and tumor necrosis factor alpha. In vitro, in VICs isolated from AVs, Gal‐3 induced expression of inflammatory, fibrotic, and osteogenic markers through the extracellular signal‐regulated kinase 1 and 2 pathway. Gal‐3 expression was blocked in VICs undergoing osteoblastic differentiation using its pharmacological inhibitor, modified citrus pectin, or the clustered regularly interspaced short palindromic repeats/Cas9 knockout system. Gal‐3 blockade and knockdown decreased the expression of inflammatory, fibrotic, and osteogenic markers in differentiated VICs. ConclusionsGal‐3, which is overexpressed in AVs from AS patients, appears to play a central role in calcification in AS. Gal‐3 could be a new therapeutic approach to delay the progression of AV calcification in AS.https://www.ahajournals.org/doi/10.1161/JAHA.116.004360aortic stenosiscalcificationgalectin‐3inflammationvalvevalvular interstitial cells |
| spellingShingle | J. Rafael Sádaba Ernesto Martínez‐Martínez Vanessa Arrieta Virginia Álvarez Amaya Fernández‐Celis Jaime Ibarrola Amaia Melero Patrick Rossignol Victoria Cachofeiro Natalia López‐Andrés Role for Galectin‐3 in Calcific Aortic Valve Stenosis Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease aortic stenosis calcification galectin‐3 inflammation valve valvular interstitial cells |
| title | Role for Galectin‐3 in Calcific Aortic Valve Stenosis |
| title_full | Role for Galectin‐3 in Calcific Aortic Valve Stenosis |
| title_fullStr | Role for Galectin‐3 in Calcific Aortic Valve Stenosis |
| title_full_unstemmed | Role for Galectin‐3 in Calcific Aortic Valve Stenosis |
| title_short | Role for Galectin‐3 in Calcific Aortic Valve Stenosis |
| title_sort | role for galectin 3 in calcific aortic valve stenosis |
| topic | aortic stenosis calcification galectin‐3 inflammation valve valvular interstitial cells |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.116.004360 |
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