Galectin-1 Controls Cardiac Inflammation and Ventricular Remodeling during Acute Myocardial Infarction

• Published in: The American journal of pathology Vol. 182; no. 1; pp. 29 - 40
• Main Authors: Seropian, Ignacio M, Cerliani, Juan P, Toldo, Stefano, Van Tassell, Benjamín W, Ilarregui, Juan M, González, Germán E, Matoso, Mirian, Salloum, Fadi N, Melchior, Ryan, Gelpi, Ricardo J, Stupirski, Juan C, Benatar, Alejandro, Gómez, Karina A, Morales, Celina, Abbate, Antonio, Rabinovich, Gabriel A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2013; American Society for Investigative Pathology
• Subjects: Adult; Aged; Animals; Apoptosis - drug effects; Apoptosis - physiology; Cell Hypoxia - physiology; Cells, Cultured; Cytokines - pharmacology; Female; Galectin 1 - biosynthesis; Galectin 1 - pharmacology; Galectin 1 - physiology; Galectin 1 - therapeutic use; Heart Failure - metabolism; Heart Failure - physiopathology; Heart Rate - drug effects; Heart Rate - physiology; Humans; Inflammation Mediators - pharmacology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Myocardial Infarction - complications; Myocardial Infarction - drug therapy; Myocardial Infarction - metabolism; Myocardial Infarction - physiopathology; Myocarditis - etiology; Myocarditis - metabolism; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Pathology; Recombinant Proteins - therapeutic use; Up-Regulation - drug effects; Up-Regulation - physiology; Ventricular Function, Left - physiology; Ventricular Remodeling - physiology; Young Adult
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/j.ajpath.2012.09.022

Galectin-1 (Gal-1), an evolutionarily conserved β-galactoside-binding lectin, plays essential roles in the control of inflammation and neovascularization. Although identified as a major component of the contractile apparatus of cardiomyocytes, the potential role of Gal-1 in modulating heart pathophysiology is uncertain. Here, we aimed to characterize Gal-1 expression and function in the infarcted heart. Expression of Gal-1 was substantially increased in the mouse heart 7 days after acute myocardial infarction (AMI) and in hearts from patients with end-stage chronic heart failure. This lectin was localized mainly in cardiomyocytes and inflammatory infiltrates in peri-infarct areas, but not in remote areas. Both simulated hypoxia and proinflammatory cytokines selectively up-regulated Gal-1 expression in mouse cardiomyocytes, whereas anti-inflammatory cytokines inhibited expression of this lectin or had no considerable effect. Compared with their wild-type counterpart, Gal-1-deficient ( Lgals1 −/− ) mice showed enhanced cardiac inflammation, characterized by increased numbers of macrophages, natural killer cells, and total T cells, but reduced frequency of regulatory T cells, leading to impaired cardiac function at baseline and impaired ventricular remodeling 7 days after nonreperfused AMI. Treatment of mice with recombinant Gal-1 attenuated cardiac damage in reperfused AMI. Taken together, our results indicate a protective role for Gal-1 in normal cardiac homeostasis and postinfarction remodeling by preventing cardiac inflammation. Thus, Gal-1 treatment represents a potential novel strategy to attenuate heart failure in AMI.