Galectin-3 Mediated Cardiovascular Fibrogenesis: An Important Cause of Heart Failure and Cardiovascular Mortality

Cardiac remodeling is the heart’s primary adaptive response to injury. Remodeling is characterized by myocyte hypertrophy, but fibrosis formation in the interstitial space is also dominant. It has been established that galectin-3 plays an important role in tissue inflammation, immunity, and fibrosis. Galectin-3 is highly upregulated in adverse cardiac remodeling and heart failure (HF). Several lines of evidence suggest that galectin-3 is not only a marker (bystander) in cardiac remodeling but it may actively contribute as well. First, plasma galectin-3 is increased in human subjects prone to develop HF, and in patients with established HF galectin-3 has emerged as a useful biomarker reflecting the severity of HF. Second, galectin-3 has been shown to contribute to the formation of fibrosis (fibrogenesis) – administering exogenous galectin-3 leads to cardiac fibrosis. Reversely, disruption of galectin-3 is associated with the absence of cardiac fibrosis. The effects of galectin-3 on fibrosis have also been established in other organs, for instance kidney and liver. Since complete (genetic) disruption is not clinically feasible, pharmacological inhibition of galectin-3 is an attractive therapeutic modality to inhibit cardiac remodeling and HF development. Various food products, containing oligosaccharides such as pectins, may act as neutralizing ligands or inhibitors for galectin-3. Pectins can bind to galectin-3’s carbohydrate recognition domain (CRD) and have been shown to inhibit carcinogenesis and other galectin-3-driven diseases. Recently, it has been reported that cardiac remodeling, fibrogenesis and HF development may also be amenable to inhibition of galectin-3. Circumstantial evidence for a potential role of galectin-3 comes from the observation that consumption of dietary fibers, e.g. from cereals and fruits, that are rich in pectins, has consistently been associated with a lower risk for heart disease. The search for the precise mechanism of galectin-3 in HF and better treatment aimed against galectin-3 is ongoing. Candidate anti-galectin-3 treatments will first have to be tested in animal models, and should then be further evaluated in clinical trials.