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

Abstract

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.

Towards molecular mechanisms regulating the expression of galectins in cancer cells under microenvironmental stress conditions

“…For example, galectin-1 expression was found to be controlled by HIF-1a in colorectal carcinoma [44], by C/EBPa in acute myeloid leukemia [45], by AP-1 in classical Hodgkin lymphoma [46], and by ROS and NF-kB in Kaposi's sarcoma [42] cells. Other lines of evidence supporting the hypoxia-induced upregulation of galectin-1 have recently been reported in a model of acute myocardial infarction considering the hypoxic microenvironment in infarcted hearts [47]. In particular, the exposure of HL-1 cardiomyocytes in a cell culture to hypoxia (1 % O 2 , 18 h) or pro-inflammatory cytokines (IL-17, TNF-a, IFN-c) increased the respective levels of galectin-1 in total cell lysates or cell culture media.…”

Adaptive Immune Responses During Pregnancy

“…Galectin-1, expressed in T and B cells, inflammatory macrophages tolerogenic DCs, uterine NK cells, uterine MCs, and Treg, gained much attention over the last 5 years in the reproduction research field. Gal-1 is known to define autoimmunity, 70 inflammatory neurodegeneration, 71 cardiac inflammation, 72 and tumor escape. 73 74 and recent data confirm that it is not only expressed by the placenta itself 75 but also in uterine NK cells, 76 tolerogenic DCs, 55 and recent data show its importance when expressed in uterine MCs.…”

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

“…15,16 Over the past decade, clinical studies have documented marked elevations of circulating galectin-3 concentrations in patients with heart failure 17 and have generated significant interest in the role of galectin-3 as a biomarker. In patients with acute or chronic heart failure, plasma galectin-3 concentrations were shown to predict mortality and adverse outcome in a variety of clinical settings.…”