{"doi":"10.1161/atvbaha.121.317735","title":"Endogenous SOD2 (Superoxide Dismutase) Regulates Platelet-Dependent Thrombin Generation and Thrombosis During Aging","abstract":"BACKGROUND: Reactive oxygen species (ROS) contribute to platelet hyperactivation during aging. Several oxidative pathways and antioxidant enzymes have been implicated; however, their mechanistic contributions during aging remain elusive. We hypothesized that mitochondria are an important source of platelet ROS and that mitochondrial SOD2 (superoxide dismutase) protects against mitochondrial ROS-driven platelet activation and thrombosis during aging. METHODS: ) mice at young (4-5 months) or old (18-20 months) ages. We examined agonist-induced platelet activation, platelet-dependent thrombin generation potential, and susceptibility to in vivo thrombosis. RESULTS: β3 activation, aggregation, and adhesion were increased to similar extents in aged mice of both genotypes compared with young mice. In contrast, the age-dependent increases in mitochondrial and total cellular ROS, calcium elevation, and phosphatidylserine exposure were augmented in platelets from pSOD2-KO mice compared with control mice. Aged pSOD2-KO mice showed increased platelet-dependent thrombin generation compared with aged control mice. In vivo, aged pSOD2-KO mice exhibited enhanced susceptibility to carotid artery and pulmonary thrombosis compared to aged control mice. Adoptive transfer of platelets from aged pSOD2-KO but not aged control mice increased thrombotic susceptibility in aged host mice, suggesting a prothrombotic effect of platelet pSOD2 deficiency. Treatment with avasopasem manganese (GC4419), a SOD mimetic, decreased platelet mitochondrial pro-oxidants, cellular ROS levels, and inhibited procoagulant platelet formation and arterial thrombosis in aged mice. CONCLUSIONS: Platelet mitochondrial ROS contributes to age-related thrombosis and endogenous SOD2 protects from platelet-dependent thrombin generation and thrombosis during aging.","journal":"Arteriosclerosis Thrombosis and Vascular Biology","year":2022,"id":247563,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":33,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9605,"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":883378,"name":"Alicia S. Eustes","orcid":"0000-0001-9436-198X","position":1,"is_corresponding":false},{"id":885635,"name":"Azaj Ahmed","orcid":"0000-0002-0876-9151","position":2,"is_corresponding":false},{"id":495375,"name":"Melissa Jensen","orcid":"0000-0002-9830-076X","position":3,"is_corresponding":false},{"id":886337,"name":"Mitali V. Solanki","orcid":null,"position":4,"is_corresponding":false},{"id":886338,"name":"Jagadish Swamy","orcid":null,"position":5,"is_corresponding":false},{"id":746931,"name":"Rahul Kumar","orcid":"0000-0002-3603-7572","position":6,"is_corresponding":false},{"id":350114,"name":"Trevor P. Fidler","orcid":"0000-0002-0758-9984","position":7,"is_corresponding":false},{"id":521131,"name":"Jon C. D. Houtman","orcid":"0000-0002-5307-9854","position":8,"is_corresponding":false},{"id":393437,"name":"Bryan G. Allen","orcid":"0000-0002-4893-7105","position":9,"is_corresponding":false},{"id":297605,"name":"Douglas R. Spitz","orcid":"0000-0002-1254-8765","position":10,"is_corresponding":false},{"id":153753,"name":"E. Dale Abel","orcid":"0000-0001-5290-0738","position":11,"is_corresponding":false},{"id":626037,"name":"Sanjana Dayal","orcid":"0000-0001-6156-2996","position":12,"is_corresponding":false},{"id":885634,"name":"Vijay K. Sonkar","orcid":"0000-0001-8511-4717","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T00:23:57.824223Z","pmid":"36325902","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":[]}