{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen Y"],"funding":["NHLBI NIH HHS","National Natural Science Foundation of China","NIH"],"pagination":["3556-3574"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9989600"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["43(37)"],"pubmed_abstract":["<h4>Aims</h4>Galectin-3, a β-galactoside-binding lectin, is abnormally increased in cardiovascular disease. 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.<h4>Methods and results</h4>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-/- 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-/- mice, which spontaneously developed increased plasma Galectin-3 levels. TD139 also suppressed microvascular thrombosis to protect the heart from myocardial ischaemia-reperfusion injury in ApoE-/- mice.<h4>Conclusion</h4>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."],"journal":["European heart journal"],"pubmed_title":["Galectin 3 enhances platelet aggregation and thrombosis via Dectin-1 activation: a translational study."],"pmcid":["PMC9989600"],"funding_grant_id":["R00 HL153678","81800305","81770137","81970305","81803522","81573423"],"pubmed_authors":["Zheng Y","Yang J","Wu M","Fan Z","Fu W","Li Q","Zhang S","Liu Y","Qi Z","Dong J","Chen Y","Gao W","Hu L","Ding Z","Yin K"],"additional_accession":[]},"is_claimable":false,"name":"Galectin 3 enhances platelet aggregation and thrombosis via Dectin-1 activation: a translational study.","description":"<h4>Aims</h4>Galectin-3, a β-galactoside-binding lectin, is abnormally increased in cardiovascular disease. 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.<h4>Methods and results</h4>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-/- 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-/- mice, which spontaneously developed increased plasma Galectin-3 levels. TD139 also suppressed microvascular thrombosis to protect the heart from myocardial ischaemia-reperfusion injury in ApoE-/- mice.<h4>Conclusion</h4>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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2024-11-11T18:59:32.676Z","creation":"2024-11-11T18:59:32.676Z"},"accession":"S-EPMC9989600","cross_references":{"pubmed":["35165707"],"doi":["10.1093/eurheartj/ehac034"]}}