{"doi":"10.1126/sciadv.adj1019","title":"Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice","abstract":"While neutrophil extracellular traps (NETs) have previously been linked to some diabetes-associated complications, such as dysfunctional wound healing, their potential role in diabetic vascular dysfunction has not been studied. Diabetic Akita mice were crossed with either Elane −/− or Pad4 −/− mice to generate NET-deficient diabetic mice. By 24 weeks of age, Akita aortae showed markedly impaired relaxation in response to acetylcholine, indicative of vascular dysfunction. Both Akita- Elane −/− mice and Akita- Pad4 −/− mice had reduced levels of circulating NETs and improved acetylcholine-mediated aortic relaxation. Compared with wild-type aortae, the thromboxane metabolite TXB 2 was roughly 10-fold higher in both intact and endothelium-denuded aortae of Akita mice. In contrast, Akita- Elane −/− and Akita- Pad4 −/− aortae had TXB 2 levels similar to wild type. In summary, inhibition of NETosis by two independent strategies prevented the development of vascular dysfunction in diabetic Akita mice. Thromboxane was up-regulated in the vessel walls of NETosis-competent diabetic mice, suggesting a role for neutrophils in driving the production of this vasoconstrictive and atherogenic prostanoid.","journal":"Science Advances","year":2023,"id":325207,"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":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105691,"name":"Srilakshmi Yalavarthi","orcid":"0009-0005-9128-572X","position":1,"is_corresponding":false},{"id":902802,"name":"Ajay Tambralli","orcid":"0000-0001-9056-9513","position":2,"is_corresponding":false},{"id":302450,"name":"Lixia Zeng","orcid":"0009-0008-1650-7929","position":3,"is_corresponding":false},{"id":1042716,"name":"Christine E. Rysenga","orcid":"0000-0002-3528-7967","position":4,"is_corresponding":false},{"id":1043387,"name":"Nikoo Alizadeh","orcid":null,"position":5,"is_corresponding":false},{"id":1042717,"name":"Lucas Hudgins","orcid":"0009-0002-7850-7250","position":6,"is_corresponding":false},{"id":471094,"name":"Wenying Liang","orcid":"0000-0001-9985-6674","position":7,"is_corresponding":false},{"id":1042718,"name":"Somanathapura K. NaveenKumar","orcid":"0000-0002-8991-5041","position":8,"is_corresponding":false},{"id":109631,"name":"Hui Shi","orcid":"0000-0002-3574-8807","position":9,"is_corresponding":false},{"id":342390,"name":"Miriam A. Shelef","orcid":"0000-0002-8842-0303","position":10,"is_corresponding":false},{"id":433355,"name":"Kevin B. Atkins","orcid":null,"position":11,"is_corresponding":false},{"id":263300,"name":"Subramaniam Pennathur","orcid":"0000-0003-3628-6883","position":12,"is_corresponding":false},{"id":105701,"name":"Jason S. Knight","orcid":"0000-0003-0995-9771","position":13,"is_corresponding":false},{"id":691228,"name":"Chao Liu","orcid":"0000-0002-7263-5289","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T01:08:22.919783Z","pmid":"37878711","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":[]}