{"doi":"10.1101/2020.10.05.325688","title":"Precision Targeting of the Plasminogen Activator Inhibitor-1 Mechanism Increases Efficacy of Fibrinolytic Therapy in Empyema","abstract":"Abstract Plasminogen activator inhibitor-1 (PAI-1) is an endogenous irreversible inhibitor of tissue-type (tPA) and urokinase (uPA) plasminogen activators. PAI-1-targeted fibrinolytic therapy (PAI-1-TFT) is designed to decrease the therapeutic dose of tPA and uPA to attenuate the risk of bleeding and other complications. The docking site peptide (DSP) is a part of the PAI-1 reactive center loop, which interacts with plasminogen activators, thus affecting the PAI-1 mechanism. We used DSP for PAI-1-TFT in two rabbit models: chemically-induced pleural injury and Streptococcus pneumoniae induced empyema. PAI-1-TFT with DSP combined with single chain uPA or tPA resulted in an up to 8-fold decrease in the minimal effective therapeutic dose of plasminogen activator and induced no bleeding. An increase in the level of PAI-1 in infectious pleural injury, when compared to chemically-induced injury, coincided with an increase in the minimal effective dose of plasminogen activator and DSP. PAI-1 is a valid molecular target in S. pneumoniae empyema model in rabbits, which closely recapitulates key characteristics of empyema in humans. Low dose PAI-1-TFT is a novel precise interventional strategy that may improve fibrinolytic therapy of empyema in clinical practice.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":131159,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":584536,"name":"R. Girard","orcid":"0000-0003-4988-7477","position":1,"is_corresponding":false},{"id":584537,"name":"Ali Azghani","orcid":"0000-0002-7626-5967","position":2,"is_corresponding":false},{"id":585100,"name":"Krishna Sarva","orcid":null,"position":3,"is_corresponding":false},{"id":585101,"name":"Ann M. Buchanan","orcid":null,"position":4,"is_corresponding":false},{"id":585102,"name":"Sophia Karandashova","orcid":null,"position":5,"is_corresponding":false},{"id":585103,"name":"Christian J. DeVera","orcid":null,"position":6,"is_corresponding":false},{"id":585104,"name":"D.E. Morris","orcid":null,"position":7,"is_corresponding":false},{"id":585105,"name":"Mignote Chamiso","orcid":null,"position":8,"is_corresponding":false},{"id":585106,"name":"Kathleen Koenig","orcid":null,"position":9,"is_corresponding":false},{"id":238005,"name":"Douglas B. Cines","orcid":"0000-0001-5986-504X","position":10,"is_corresponding":false},{"id":501233,"name":"Steven Idell","orcid":"0000-0003-4389-2152","position":11,"is_corresponding":false},{"id":559449,"name":"Andrey A. Komissarov","orcid":"0000-0003-4346-8888","position":12,"is_corresponding":false},{"id":585099,"name":"Galina Florova","orcid":null,"position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:16:00.235845Z","pmid":null,"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":[]}