Expression, Localization and Actions of Galectin-3: Implications in the Pathophysiology and Therapy of Cardiovascular Disease

Research in the last two decades has well established galectin-3 (Gal3), a member of the lectin family, as a clinical biomarker and mediator of cardiovascular as well as other diseases. Gal3 contributes to progression of diseases by promoting pathological components, including inflammation, fibrosis, cell death or proliferation, and metabolic remodeling, and hence forms an ideal therapeutic target. Notably, nearly all Gal3 inhibitors that are currently under intensive pre-clinical and clinical testing target carbohydrate recognition/binding domain (CRD) of Gal3 molecules. Whereas the role of Gal3 in cardiovascular disease (CVD) has been well established, research on Gal3 in cancer or immunology has been leading the frontiers in this discipline. Therefore, it is important to have an integrated understanding on the biology and pathophysiology of Gal3 in a spectrum of pathological conditions. This review describes current findings from studies on diverse disease conditions and examines the role of Gal3 in the pathogenesis of diseases focusing on its transcription, post-translational modifications, intracellular dynamics, extracellular exporting, and interactions with a variety of signaling molecules. By bridging findings from different disciplines on the role of Gal3 in diseased settings, we explore the diverse anti-Gal3 strategies in addition to inhibition of CRD binding and highlight the significance of interventions targeting the transcription and post-translational modifications of Gal3, as well as intracellular actions of Gal3. At the end of this review, we provide perspectives for future research and therapeutic implications in CVD.