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Plasma Galectin-3 receives a Class II recommendation for heart failure management and has been extensively studied for multiple cellular functions. The direct effects of Galectin-3 on platelet activation remain unclear. This study explores the direct effects of Galectin-3 on platelet activation and thrombosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>A strong positive correlation between plasma Galectin-3 concentration and platelet aggregation or whole blood thrombus formation was observed in patients with coronary artery disease (CAD). Multiple platelet function studies demonstrated that Galectin-3 directly potentiated platelet activation and in vivo thrombosis. Mechanistic studies using the Dectin-1 inhibitor, laminarin, and Dectin-1\u2212\/\u2212 mice revealed that Galectin-3 bound to and activated Dectin-1, a receptor not previously reported in platelets, to phosphorylate spleen tyrosine kinase and thus increased Ca2+ influx, protein kinase C activation, and reactive oxygen species production to regulate platelet hyperreactivity. TD139, a Galectin-3 inhibitor in a Phase II clinical trial, concentration dependently suppressed Galectin-3-potentiated platelet activation and inhibited occlusive thrombosis without exacerbating haemorrhage in ApoE\u2212\/\u2212 mice, which spontaneously developed increased plasma Galectin-3 levels. TD139 also suppressed microvascular thrombosis to protect the heart from myocardial ischaemia\u2013reperfusion injury in ApoE\u2212\/\u2212 mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Galectin-3 is a novel positive regulator of platelet hyperreactivity and thrombus formation in CAD. As TD139 has potent antithrombotic effects without bleeding risk, Galectin-3 inhibitors may have therapeutic advantages as potential antiplatelet drugs for patients with high plasma Galectin-3 levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehac034","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T07:22:08Z","timestamp":1643095328000},"page":"3556-3574","source":"Crossref","is-referenced-by-count":58,"title":["Galectin 3 enhances platelet aggregation and thrombosis via Dectin-1 activation: a translational study"],"prefix":"10.1093","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4346-6391","authenticated-orcid":false,"given":"Yufei","family":"Chen","sequence":"first","affiliation":[{"name":"Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine , Shanghai 201203 , China"},{"name":"Department of Cardiology, Huashan Hospital, Fudan University , Shanghai , 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