title: Myocardial Galectin-3 Expression Is Associated with Remodeling of the Pressure-Overloaded Heart and May Delay the Hypertrophic Response without Affecting Survival, Dysfunction, and Cardiac Fibrosis.
abstract: The β-galactoside-binding animal lectin galectin-3 is predominantly expressed by activated macrophages and is a promising biomarker for patients with heart failure. Galectin-3 regulates inflammatory and fibrotic responses; however, its role in cardiac remodeling remains unclear. We hypothesized that galectin-3 may be up-regulated in the pressure-overloaded myocardium and regulate hypertrophy and fibrosis. In normal mouse myocardium, galectin-3 was constitutively expressed in macrophages and was localized in atrial but not ventricular cardiomyocytes. In a mouse model of transverse aortic constriction, galectin-3 expression was markedly up-regulated in the pressure-overloaded myocardium. Early up-regulation of galectin-3 was localized in subpopulations of macrophages and myofibroblasts; however, after 7 to 28 days of transverse aortic constriction, a subset of cardiomyocytes in fibrotic areas contained large amounts of galectin-3. In vitro, cytokine stimulation suppressed galectin-3 synthesis by macrophages and cardiac fibroblasts. Correlation studies revealed that cardiomyocyte- but not macrophage-specific galectin-3 localization was associated with adverse remodeling and dysfunction. Galectin-3 knockout mice exhibited accelerated cardiac hypertrophy after 7 days of pressure overload, whereas female galectin-3 knockouts had delayed dilation after 28 days of transverse aortic constriction. However, galectin-3 loss did not affect survival, systolic and diastolic dysfunction, cardiac fibrosis, and cardiomyocyte hypertrophy in the pressure-overloaded heart. Despite its potential role as a prognostic biomarker, galectin-3 is not a critical modulator of cardiac fibrosis but may delay the hypertrophic response.
authors.affiliation: Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Olga
authors.initials: O
authors.lastname: Frunza
authors.affiliation: Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Russo
authors.affiliation: Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Amit
authors.initials: A
authors.lastname: Saxena
authors.affiliation: Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Arti V
authors.initials: AV
authors.lastname: Shinde
authors.affiliation: Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Claudio
authors.initials: C
authors.lastname: Humeres
authors.affiliation: Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Waqas
authors.initials: W
authors.lastname: Hanif
authors.affiliation: Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Vikrant
authors.initials: V
authors.lastname: Rai
authors.affiliation: Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Ya
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York. Electronic address: nikolaos.frangogiannis@einstein.yu.edu.
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Frangogiannis
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000503:physiopathology*; D015150:Echocardiography, Doppler; D004719:Endomyocardial Fibrosis / Q000000981:diagnostic imaging / Q000503:physiopathology; D005260:Female; D037502:Galectin 3 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D058628:Myofibroblasts / Q000378:metabolism / Q000502:physiology; D051900:Smad3 Protein / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D015415:Biomarkers; D037502:Galectin 3; D053583:Interleukin-1beta; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta