Galectin-3 as a therapeutic target in pulmonary hypertension: Molecular mechanisms, drug development directions, and emerging clinical applications

Pulmonary hypertension (PH) remains a devastating cardiovascular disorder with limited targeted treatment. Galectin-3 has emerged as a promising therapeutic target due to its central role in vascular remodeling and inflammation. Galectin-3 exacerbates intimal hyperplasia by influencing endothelial cells through multiple mechanisms. It also contributes to medial hypertrophy and adventitial thickening by activating vascular smooth muscle cells and adventitial fibroblasts. In PH, right ventricular myocardium can be remodeled through galectin-3-mediated activation of cardiac fibroblasts and impaired cardiomyocyte contractility. Galectin-3 also modulates accompanying inflammatory reactions. This review explores the molecular mechanisms of galectin-3 action in PH and evaluates the potential of galectin-3 inhibition as a therapeutic strategy. Targeting galectin-3 represents a novel avenue in PH management but still faces challenges such as drug specificity and clinical efficacy. Future studies should focus on optimizing the structure and performance of galectin-3 inhibitors for clinical application.