Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity.
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.
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.
Ernesto
E
Martínez-Martínez
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.
Natalia
N
López-Ándres
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.
Raquel
R
Jurado-López
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.
Elodie
E
Rousseau
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.
Mará Visitación
MV
Bartolomé
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.
Amaya
A
Fernández-Celis
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.
Patrick
P
Rossignol
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.
Fabian
F
Islas
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.
Alfonso
A
Antequera
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.
Santiago
S
Prieto
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.
María
M
Luaces
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.
Victoria
V
Cachofeiro
D000328:Adult; D000818:Animals; D002319:Cardiovascular System / Q000503:physiopathology*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000453:epidemiology; D037502:Galectin 3 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000503:physiopathology*; D015994:Incidence; D007249:Inflammation / Q000453:epidemiology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D009765:Obesity / Q000150:complications* / Q000209:etiology / Q000503:physiopathology*; D010368:Pectins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000502:physiology*
D037502:Galectin 3; D010368:Pectins
fibrosis; galectin-3; inflammation; obesity; vascular stiffness