Galectin-3 induced platelet aggregation

Background/Introduction Galectin-3 (Gal-3) is a multifunctional protein implicated in diverse biological processes, including inflammation, fibrosis, and metabolic dysregulation, and it plays a significant role in cardiovascular disease, notably as atherosclerosis and acute coronary syndromes. Gal-3 enhances platelet aggregation and thrombosis via activation of Dectin-1 receptors, contributing to cardiovascular risk, particularly in high-risk patients. Purpose This study aimed to evaluate the effects of a Galectin-3 inhibitor (Gal-3I) on platelet aggregation in patients with acute coronary syndrome (ACS), stable angina, and metabolic risk factors, investigating the role of Gal-3 in modulating platelet hyperreactivity. Methods Platelet aggregation was conducted using a two-component assay with classical agonists (ADP and epinephrine) alone and in combination with Gal-3I, on venous and arterial blood samples from patient cohorts. The study included assessments across gender, age, and diabetes status. Statistical analyses adjusted for confounders were performed to evaluate aggregation responses. Mann-Whitney and KruskalWallis tests were used. Results ACS patients exhibited significantly (p<0.05) lower platelet aggregation in response to ADP (venous blood) when combined with Gal-3I compared to stable angina and high-risk groups (median (min-max), 51 (11- 94)%agr vs 60 (6-90)%agr vs 64 (0-91)%agr, respectively).. No significant gender differences were found, though a trend of declining platelet function with age was noted in females. Gal-3I normalized platelet aggregation levels between patients with diabetes and control subjects, supporting its role in reducing platelet hyperreactivity linked with metabolic disorders. Conclusion(s) Galectin-3 is a critical modulator of platelet function, particularly in acute cardiovascular events and metabolic disease contexts. Inhibition of Gal-3 attenuates platelet hyperactivity and may represent a promising therapeutic avenue for reducing thrombotic risk in ischemic heart disease. Further research is warranted to clarify underlying pathways and optimize therapeutic strategies.