Tags

Type your tag names separated by a space and hit enter

Role for Galectin-3 in Calcific Aortic Valve Stenosis.
J Am Heart Assoc 2016; 5(11)JA

Abstract

BACKGROUND

Aortic 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 RESULTS

Blood 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.

CONCLUSIONS

Gal-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.

Authors+Show Affiliations

Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116, CHRU de Nancy, Université de Lorraine French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT, Nancy, France.Department of Physiology, School of Medicine, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense, Madrid, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain natalia.lopez.andres@navarra.es. INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116, CHRU de Nancy, Université de Lorraine French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT, Nancy, France.

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

27815266

Citation

Sádaba, J Rafael, et al. "Role for Galectin-3 in Calcific Aortic Valve Stenosis." Journal of the American Heart Association, vol. 5, no. 11, 2016.
Sádaba JR, Martínez-Martínez E, Arrieta V, et al. Role for Galectin-3 in Calcific Aortic Valve Stenosis. J Am Heart Assoc. 2016;5(11).
Sádaba, J. R., Martínez-Martínez, E., Arrieta, V., Álvarez, V., Fernández-Celis, A., Ibarrola, J., ... López-Andrés, N. (2016). Role for Galectin-3 in Calcific Aortic Valve Stenosis. Journal of the American Heart Association, 5(11).
Sádaba JR, et al. Role for Galectin-3 in Calcific Aortic Valve Stenosis. J Am Heart Assoc. 2016 11 4;5(11) PubMed PMID: 27815266.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role for Galectin-3 in Calcific Aortic Valve Stenosis. AU - Sádaba,J Rafael, AU - Martínez-Martínez,Ernesto, AU - Arrieta,Vanessa, AU - Álvarez,Virginia, AU - Fernández-Celis,Amaya, AU - Ibarrola,Jaime, AU - Melero,Amaia, AU - Rossignol,Patrick, AU - Cachofeiro,Victoria, AU - López-Andrés,Natalia, Y1 - 2016/11/04/ PY - 2016/11/6/entrez PY - 2016/11/7/pubmed PY - 2017/12/20/medline KW - aortic stenosis KW - calcification KW - galectin‐3 KW - inflammation KW - valve KW - valvular interstitial cells JF - Journal of the American Heart Association JO - J Am Heart Assoc VL - 5 IS - 11 N2 - BACKGROUND: Aortic 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 RESULTS: Blood 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. CONCLUSIONS: Gal-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. SN - 2047-9980 UR - https://www.unboundmedicine.com/medline/citation/27815266/Role_for_Galectin_3_in_Calcific_Aortic_Valve_Stenosis_ L2 - http://www.ahajournals.org/doi/full/10.1161/JAHA.116.004360?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -