GALECTIN-1 CONTROLS CARDIAC INFLAMMATION AND VENTRICULAR REMODELING DURING ACUTE MYOCARDIAL INFARCTION

SEROPIAN IGNACIO; CERLIANI JUAN PABLO; TOLDO STEFANO; VAN TASSEL BENJAMIN; ILARREGUI JUAN; GONZALEZ GERMÁN; MATOSO MIRIAM; SALLOUM FADI; MELCHIOR RYAN; GELPI RICARDO; STUPIRSKI JUAN CARLOS; BENATAR ALEJANDRO; GOMEZ KARINA; MORALES CELINA; ABBATE ANTONIO; RABINOVICH GABRIEL

AMERICAN JOURNAL OF PATHOLOGY

AMER SOC INVESTIGATIVE PATHOLOGY, INC

Lugar: Bethesda ; Año: 2013 vol. 182 p. 29 - 40

0002-9440

Galectin-1 (Gal-1), an evolutionarily conserved -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 mainly localized in cardiomyocytes and inflammatory infiltrates in peri-infarct areas but not in remote areas. Simulated hypoxia as well as pro-inflammatory 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 to their wild-type (WT) counterpart, Gal-1-deficient (Lgals1-/-) mice showed enhanced cardiac inflammation characterized by increased number 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 non-reperfused AMI. Treatment of mice with recombinant Gal-1 attenuated cardiac damage in reperfused AMI. Collectively, our results indicate a protective role for Gal-1 in normal cardiac homeostasis and post-infarction remodeling by preventing cardiac inflammation. Thus, Gal-1 treatment represents a potential novel strategy to attenuate heart failure in AMI.