Galectin-1 controls cardiac inflammation and ventricular remodeling during acute myocardial infarction

SEROPIAN IM; CERLIANI JP; TOLDO S; VAN TASSELL BW; ILARREGUI JM; GONZALEZ GE; MATOSO M; SALLOUM FN; MELCHIOR R; GELPI RJ; STUPIRSKI JC; BENATAR A; GÓMEZ KA; MORALES C; ABBATE A; RABINOVICH GA

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 b-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. (Am J Pathol 2012, -: 1e12; http://dx.doi.org/10.1016/j.ajpath.2012.09.022)