{"doi":"10.1124/jpet.105.093450","title":"Fibrin Affinity of Erythrocyte-Coupled Tissue-Type Plasminogen Activators Endures Hemodynamic Forces and Enhances Fibrinolysis in Vivo","abstract":null,"journal":"The Journal of Pharmacology and Experimental Therapeutics","year":2006,"id":669900,"datarank":0.5333022092234121,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.0,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1749626,"name":"Mukul S. Goel","orcid":null,"position":1,"is_corresponding":false},{"id":1749627,"name":"Tatyana Krasik","orcid":null,"position":2,"is_corresponding":false},{"id":460029,"name":"Khalil Bdeir","orcid":null,"position":3,"is_corresponding":false},{"id":371179,"name":"Scott L. Diamond","orcid":"0000-0002-9791-2238","position":4,"is_corresponding":false},{"id":238005,"name":"Douglas B. Cines","orcid":"0000-0001-5986-504X","position":5,"is_corresponding":false},{"id":266256,"name":"Vladimir R. Muzykantov","orcid":"0000-0001-6648-1204","position":6,"is_corresponding":false},{"id":1749628,"name":"Juan-Carlos Murciano","orcid":null,"position":7,"is_corresponding":false},{"id":1437015,"name":"Kumkum Ganguly","orcid":"0000-0002-2255-8940","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Fibrin Affinity of Erythrocyte-Coupled Tissue-Type Plasminogen Activators Endures Hemodynamic Forces and Enhances Fibrinolysis in Vivo","abstract":"Plasminogen activators (PAs; e.g., tissue-type, tPA) coupled to red blood cells (RBCs) display in vivo features useful for thromboprophylaxis: prolonged circulation, minimal extravasation, and preferential lysis of nascent versus preexisting clots. Yet, factors controlling the activity of RBC-bound PAs in vivo are not defined and may not mirror the profile of soluble PAs. We tested the role of RBC/PA binding to fibrin in fibrinolysis. RBC/tPA and RBC/tPA variant with low fibrin affinity (rPA) bound to and lysed plasminogen-containing fibrin clots in vitro comparably. In contrast, when coinjected in mice with fibrin emboli lodging in pulmonary vasculature, only RBC/tPA accumulated in lungs, which resulted in a more extensive fibrinolysis versus RBC/rPA (p < 0.01). Reconciling this apparent divergence between in vitro and in vivo behaviors, RBC/tPA, but not RBC/rPA perfused over fibrin in vitro at physiological shear stress bound to fibrin clots and caused greater fibrinolysis versus RBC/rPA (p < 0.001). These results indicate that because of high fibrin affinity, RBC/tPA binding to clots endures hemodynamic stress, which enhances fibrinolysis. Behavior of RBC/PAs under hemodynamic pressure is an important predictor of their performance in vivo.","is_dataset_classified":null,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16284278","pmcid":null,"openalex_id":"https://openalex.org/W2059336501","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"HL60169","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL66442","title":null}],"total_grants":2,"fwci":0.8548,"citation_percentile":0.73186586,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":1},{"year":2014,"count":3},{"year":2016,"count":2},{"year":2017,"count":2},{"year":2018,"count":2},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2021,"count":3},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2025,"count":1}],"oa_status":"closed","license":"https://www.elsevier.com/legal/tdmrep-license","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0022356524325364?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0022356524325364?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1124/jpet.105.093450","host_type":"publisher"},{"url":"https://doi.org/10.1124/jpet.105.093450","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16284278","host_type":"repository"}],"fields_of_study":["Blood Coagulation and Thrombosis Mechanisms","Protease and Inhibitor Mechanisms","Acute Ischemic Stroke Management"],"mesh_terms":["Animals","Erythrocytes","Fibrin","Fibrinolysis","Hemodynamics","Humans","Male","Mice, Inbred C57BL","Tissue Plasminogen Activator","Protein Binding","Pulmonary Embolism","Mice"],"keywords":["Fibrinolysis","Fibrin","In vivo","Hemodynamics","Chemistry","Pharmacology","Internal medicine","Medicine","Biology","Immunology"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-15T08:15:53.204810Z","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":[]}