{"doi":"10.1093/eurheartj/ehac034","title":"Galectin 3 enhances platelet aggregation and thrombosis via Dectin-1 activation: a translational study","abstract":"AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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","year":2022,"id":238437,"datarank":0.6064576901751826,"base_score":4.04305126783455,"endowment":4.04305126783455,"self_citation_contribution":0.6064576901751826,"citation_network_contribution":0.0,"self_endowment_contribution":0.6064576901751826,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":56,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":862232,"name":"Wanrong Fu","orcid":"0000-0002-7521-5204","position":1,"is_corresponding":false},{"id":441108,"name":"Yunbo Zheng","orcid":null,"position":2,"is_corresponding":false},{"id":862233,"name":"Jing Yang","orcid":"0000-0001-6612-7854","position":3,"is_corresponding":false},{"id":862234,"name":"Yangyang Liu","orcid":"0000-0001-8296-7095","position":4,"is_corresponding":false},{"id":862235,"name":"Zhiyong Qi","orcid":"0000-0001-5720-4061","position":5,"is_corresponding":false},{"id":862236,"name":"Meiling Wu","orcid":"0000-0002-2654-4896","position":6,"is_corresponding":false},{"id":324388,"name":"Zhichao Fan","orcid":"0000-0001-5385-9626","position":7,"is_corresponding":false},{"id":712040,"name":"Kanhua Yin","orcid":"0000-0002-4769-3129","position":8,"is_corresponding":false},{"id":857326,"name":"Yunfeng Chen","orcid":"0000-0001-7618-107X","position":9,"is_corresponding":false},{"id":862237,"name":"Wen Gao","orcid":"0000-0002-9857-5966","position":10,"is_corresponding":false},{"id":862238,"name":"Zhongren Ding","orcid":"0000-0001-9487-4865","position":11,"is_corresponding":false},{"id":862239,"name":"Jianzeng Dong","orcid":"0000-0001-7299-7805","position":12,"is_corresponding":false},{"id":862240,"name":"Qi Li","orcid":"0000-0001-8786-3922","position":13,"is_corresponding":false},{"id":328687,"name":"Si Zhang","orcid":"0000-0002-5682-4995","position":14,"is_corresponding":false},{"id":681801,"name":"Liang Hu","orcid":"0000-0001-5559-3913","position":15,"is_corresponding":false},{"id":862231,"name":"Yufei Chen","orcid":"0000-0002-4346-6391","position":0,"is_corresponding":true}],"reference_count":96,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:22:26.932537Z","pmid":"35165707","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}