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Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity.
Hypertension 2015; 66(5):961-9H

Abstract

Remodeling, diastolic dysfunction, and arterial stiffness are some of the alterations through which obesity affects the cardiovascular system. Fibrosis and inflammation are important mechanisms underlying cardiovascular remodeling, although the precise promoters involved in these processes are still unclear. Galectin-3 (Gal-3) induces inflammation and fibrosis in the cardiovascular system. We have investigated the potential role of Gal-3 in cardiac damage in morbidly obese patients, and we have evaluated the protective effect of the Gal-3 inhibition in the occurrence of cardiovascular fibrosis and inflammation in an experimental model of obesity. Morbid obesity is associated with alterations in cardiac remodeling, mainly left ventricular hypertrophy and diastolic dysfunction. Obesity and hypertension are the main determinants of left ventricular hypertrophy. Insulin resistance, left ventricular hypertrophy, and circulating levels of C-reactive protein and Gal-3 are associated with a worsening of diastolic function in morbidly obese patients. Obesity upregulates Gal-3 production in the cardiovascular system in a normotensive animal model of diet-induced obesity by feeding for 6 weeks a high-fat diet (33.5% fat). Gal-3 inhibition with modified citrus pectin (100 mg/kg per day) reduced cardiovascular levels of Gal-3, total collagen, collagen I, transforming and connective growth factors, osteopontin, and monocyte chemoattractant protein-1 in the heart and aorta of obese animals without changes in body weight or blood pressure. In morbidly obese patients, Gal-3 levels are associated with diastolic dysfunction. In obese animals, Gal-3 blockade decreases cardiovascular fibrosis and inflammation. These data suggest that Gal-3 could be a novel therapeutic target in cardiac fibrosis and inflammation associated with obesity.

Authors+Show Affiliations

From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., N.L.-A., A.F.-C.); INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.L.-A., E.T., P.R.); Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Ophthalmology and Otolaryngology, Facultad de Psicología, Universidad Complutense, Madrid, Spain (M.V.B.); Department of Cardiology, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (F.I., M.L.); and Department of Upper Gastroenterology and Bariatric Surgery (A.A.) and Department of Clinical Analysis (S.P.), Hospital Universitario de Fuenlabrada, Madrid, Spain.From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., N.L.-A., A.F.-C.); INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.L.-A., E.T., P.R.); Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Ophthalmology and Otolaryngology, Facultad de Psicología, Universidad Complutense, Madrid, Spain (M.V.B.); Department of Cardiology, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (F.I., M.L.); and Department of Upper Gastroenterology and Bariatric Surgery (A.A.) and Department of Clinical Analysis (S.P.), Hospital Universitario de Fuenlabrada, Madrid, Spain.From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., N.L.-A., A.F.-C.); INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.L.-A., E.T., P.R.); Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Ophthalmology and Otolaryngology, Facultad de Psicología, Universidad Complutense, Madrid, Spain (M.V.B.); Department of Cardiology, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (F.I., M.L.); and Department of Upper Gastroenterology and Bariatric Surgery (A.A.) and Department of Clinical Analysis (S.P.), Hospital Universitario de Fuenlabrada, Madrid, Spain.From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., N.L.-A., A.F.-C.); INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.L.-A., E.T., P.R.); Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Ophthalmology and Otolaryngology, Facultad de Psicología, Universidad Complutense, Madrid, Spain (M.V.B.); Department of Cardiology, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (F.I., M.L.); and Department of Upper Gastroenterology and Bariatric Surgery (A.A.) and Department of Clinical Analysis (S.P.), Hospital Universitario de Fuenlabrada, Madrid, Spain.From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., N.L.-A., A.F.-C.); INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.L.-A., E.T., P.R.); Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Ophthalmology and Otolaryngology, Facultad de Psicología, Universidad Complutense, Madrid, Spain (M.V.B.); Department of Cardiology, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (F.I., M.L.); and Department of Upper Gastroenterology and Bariatric Surgery (A.A.) and Department of Clinical Analysis (S.P.), Hospital Universitario de Fuenlabrada, Madrid, Spain.From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., N.L.-A., A.F.-C.); INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.L.-A., E.T., P.R.); Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Ophthalmology and Otolaryngology, Facultad de Psicología, Universidad Complutense, Madrid, Spain (M.V.B.); Department of Cardiology, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (F.I., M.L.); and Department of Upper Gastroenterology and Bariatric Surgery (A.A.) and Department of Clinical Analysis (S.P.), Hospital Universitario de Fuenlabrada, Madrid, Spain.From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., N.L.-A., A.F.-C.); INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.L.-A., E.T., P.R.); Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Ophthalmology and Otolaryngology, Facultad de Psicología, Universidad Complutense, Madrid, Spain (M.V.B.); Department of Cardiology, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (F.I., M.L.); and Department of Upper Gastroenterology and Bariatric Surgery (A.A.) and Department of Clinical Analysis (S.P.), Hospital Universitario de Fuenlabrada, Madrid, Spain.From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., N.L.-A., A.F.-C.); INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.L.-A., E.T., P.R.); Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Ophthalmology and Otolaryngology, Facultad de Psicología, Universidad Complutense, Madrid, Spain (M.V.B.); Department of Cardiology, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (F.I., M.L.); and Department of Upper Gastroenterology and Bariatric Surgery (A.A.) and Department of Clinical Analysis (S.P.), Hospital Universitario de Fuenlabrada, Madrid, Spain.From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., N.L.-A., A.F.-C.); INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.L.-A., E.T., P.R.); Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Ophthalmology and Otolaryngology, Facultad de Psicología, Universidad Complutense, Madrid, Spain (M.V.B.); Department of Cardiology, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (F.I., M.L.); and Department of Upper Gastroenterology and Bariatric Surgery (A.A.) and Department of Clinical Analysis (S.P.), Hospital Universitario de Fuenlabrada, Madrid, Spain.From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., N.L.-A., A.F.-C.); INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.L.-A., E.T., P.R.); Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Ophthalmology and Otolaryngology, Facultad de Psicología, Universidad Complutense, Madrid, Spain (M.V.B.); Department of Cardiology, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (F.I., M.L.); and Department of Upper Gastroenterology and Bariatric Surgery (A.A.) and Department of Clinical Analysis (S.P.), Hospital Universitario de Fuenlabrada, Madrid, Spain.From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., N.L.-A., A.F.-C.); INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.L.-A., E.T., P.R.); Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Ophthalmology and Otolaryngology, Facultad de Psicología, Universidad Complutense, Madrid, Spain (M.V.B.); Department of Cardiology, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (F.I., M.L.); and Department of Upper Gastroenterology and Bariatric Surgery (A.A.) and Department of Clinical Analysis (S.P.), Hospital Universitario de Fuenlabrada, Madrid, Spain.From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., N.L.-A., A.F.-C.); INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.L.-A., E.T., P.R.); Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Ophthalmology and Otolaryngology, Facultad de Psicología, Universidad Complutense, Madrid, Spain (M.V.B.); Department of Cardiology, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (F.I., M.L.); and Department of Upper Gastroenterology and Bariatric Surgery (A.A.) and Department of Clinical Analysis (S.P.), Hospital Universitario de Fuenlabrada, Madrid, Spain. vcara@ucm.es.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26351031

Citation

Martínez-Martínez, Ernesto, et al. "Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity." Hypertension (Dallas, Tex. : 1979), vol. 66, no. 5, 2015, pp. 961-9.
Martínez-Martínez E, López-Ándres N, Jurado-López R, et al. Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity. Hypertension. 2015;66(5):961-9.
Martínez-Martínez, E., López-Ándres, N., Jurado-López, R., Rousseau, E., Bartolomé, M. V., Fernández-Celis, A., ... Cachofeiro, V. (2015). Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity. Hypertension (Dallas, Tex. : 1979), 66(5), pp. 961-9. doi:10.1161/HYPERTENSIONAHA.115.06032.
Martínez-Martínez E, et al. Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity. Hypertension. 2015;66(5):961-9. PubMed PMID: 26351031.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity. AU - Martínez-Martínez,Ernesto, AU - López-Ándres,Natalia, AU - Jurado-López,Raquel, AU - Rousseau,Elodie, AU - Bartolomé,Mará Visitación, AU - Fernández-Celis,Amaya, AU - Rossignol,Patrick, AU - Islas,Fabian, AU - Antequera,Alfonso, AU - Prieto,Santiago, AU - Luaces,María, AU - Cachofeiro,Victoria, Y1 - 2015/09/08/ PY - 2015/06/23/received PY - 2015/08/10/accepted PY - 2015/9/10/entrez PY - 2015/9/10/pubmed PY - 2016/2/13/medline KW - fibrosis KW - galectin-3 KW - inflammation KW - obesity KW - vascular stiffness SP - 961 EP - 9 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 66 IS - 5 N2 - Remodeling, diastolic dysfunction, and arterial stiffness are some of the alterations through which obesity affects the cardiovascular system. Fibrosis and inflammation are important mechanisms underlying cardiovascular remodeling, although the precise promoters involved in these processes are still unclear. Galectin-3 (Gal-3) induces inflammation and fibrosis in the cardiovascular system. We have investigated the potential role of Gal-3 in cardiac damage in morbidly obese patients, and we have evaluated the protective effect of the Gal-3 inhibition in the occurrence of cardiovascular fibrosis and inflammation in an experimental model of obesity. Morbid obesity is associated with alterations in cardiac remodeling, mainly left ventricular hypertrophy and diastolic dysfunction. Obesity and hypertension are the main determinants of left ventricular hypertrophy. Insulin resistance, left ventricular hypertrophy, and circulating levels of C-reactive protein and Gal-3 are associated with a worsening of diastolic function in morbidly obese patients. Obesity upregulates Gal-3 production in the cardiovascular system in a normotensive animal model of diet-induced obesity by feeding for 6 weeks a high-fat diet (33.5% fat). Gal-3 inhibition with modified citrus pectin (100 mg/kg per day) reduced cardiovascular levels of Gal-3, total collagen, collagen I, transforming and connective growth factors, osteopontin, and monocyte chemoattractant protein-1 in the heart and aorta of obese animals without changes in body weight or blood pressure. In morbidly obese patients, Gal-3 levels are associated with diastolic dysfunction. In obese animals, Gal-3 blockade decreases cardiovascular fibrosis and inflammation. These data suggest that Gal-3 could be a novel therapeutic target in cardiac fibrosis and inflammation associated with obesity. SN - 1524-4563 UR - https://www.unboundmedicine.com/medline/citation/26351031/Galectin_3_Participates_in_Cardiovascular_Remodeling_Associated_With_Obesity_ L2 - http://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.115.06032?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -