Galectin-1 as an Emerging Mediator of Cardiovascular Inflammation: Mechanisms and Therapeutic Opportunities.

Ignacio M Seropian,Germán E González,Gabriel A Rabinovich,Antonio Abbate,Daniel H Berrocal,Sebastián M Maller

doi:10.1155/2018/8696543

Abstract

Galectin-1 (Gal-1), an evolutionarily conserved β-galactoside-binding lectin, controls immune cell homeostasis and tempers acute and chronic inflammation by blunting proinflammatory cytokine synthesis, engaging T-cell apoptotic programs, promoting expansion of T regulatory (Treg) cells, and deactivating antigen-presenting cells. In addition, this lectin promotes angiogenesis by co-opting the vascular endothelial growth factor receptor (VEGFR) 2 signaling pathway. Since a coordinated network of immunomodulatory and proangiogenic mediators controls cardiac homeostasis, this lectin has been proposed to play a key hierarchical role in cardiac pathophysiology via glycan-dependent regulation of inflammatory responses. Here, we discuss the emerging roles of Gal-1 in cardiovascular diseases including acute myocardial infarction, heart failure, Chagas cardiomyopathy, pulmonary hypertension, and ischemic stroke, highlighting underlying anti-inflammatory mechanisms and therapeutic opportunities. Whereas Gal-1 administration emerges as a potential novel treatment option in acute myocardial infarction and ischemic stroke, Gal-1 blockade may contribute to attenuate pulmonary arterial hypertension.

Highlights

Galectins are a family of β-galactoside-binding lectins widely expressed in a variety of cells and tissues [1]
15 different members have been identified, which are classified according to their biochemical structure into three groups: (a) prototype galectins, including galectin- (Gal-) 1, -2, -5, -7, 10, -11, -13, -14, and -15, display one carbohydrate-recognition domain (CRD) and can dimerize; (b) tandem-repeat galectins, including Gal-4, -6, -8, -9, and -12, exhibit two CRDs associated with a linker peptide; and (c) the unique chimera-type Gal-3 contains one CRD and an additional nonlectin domain and can oligomerize [1]
Gal-1 expression is increased in the heart of patients with acute myocardial infarction (AMI), heart failure (HF), and Chagas cardiomyopathy

Summary

Introduction

Galectins are a family of β-galactoside-binding lectins widely expressed in a variety of cells and tissues [1]. We discuss the relevance of Gal-1 in cardiovascular disorders including acute myocardial infarction (AMI), heart failure (HF), Chagas cardiomyopathy, pulmonary hypertension (PAH), and ischemic stroke and highlight cellular and molecular mechanisms underlying these effects. Mice lacking Gal-1 (Lgals1−/−) showed adverse ventricular remodeling after AMI with increased cardiac dilation associated with dysregulated uncontrolled inflammation (Table 1) [19].

Results

Conclusion