Structured Graphical Abstract.

Working model for plasma Galectin-3 directly potentiating platelet activation, and the platelet hyperreactivity suppressing effect of Galectin-3 inhibitor TD139 in coronary artery disease. Accumulated Galectin-3 in plasma directly activates Dectin-1 receptor to potentiate platelet activation (platelet aggregation and ATP release), which enhances in vivo thrombosis and myocardial ischaemia–reperfusion injury. Galectin-3 inhibitor TD139 specifically inhibits Galectin-3-induced platelet hyperreactivity to ameliorate atherothrombosis and myocardial infarction in coronary artery disease.