Role of galectin-3 pathways in the pathogenesis of cardiac remodeling and heart failure

Myocardial injuries stemming from pressure overload or myocardial infarction lead to cardiac remodeling and represent major health problems worldwide. An ever accumulating body of experimental and clinical research appoints galectin-3, a ß-galactoside-binding lectin, as a key player in this maladaptive response to myocardial injury. Herein, a specific role for galectin-3 in inflammation and fibrogenesis has been elucidated in experimental and clinical studies. Galectin-3 was fir st associated with pathological conditions leading to cardiac remodeling, such as inflammation and fibrosis. Then, as the carbohydrate recognition domain of galectin-3 reacts with glycosylated proteins such as laminin, fibronectin, and tenascin, a multifunctional role of galectin-3 in the extracellular matrix was postulated. Notably, experimental animal studies clearly showed that galectin-3 is a mediator of crucial steps in fibrogenesis and further induces cardiac inflammation, hypertrophy, and dysfunction. Possible mechanisms pertaining to galectin-3 inflammatory and fibrotic properties have been suggested to involve macrophage activation, galectin-3-induced chemotaxis, and activation of the TGF-ß-Smad3 signaling pathways. Additionally, the link between plasma galectin-3 and fibrosis was also established in clinical biomarker studies. Galectin-3 and its pathways may be explored further in order to develop more efficient strategies to target cardiac remodeling in heart failure leading to fibrosis.