{"doi":"10.1161/strokeaha.117.017305","title":"Vascular Tissue-Type Plasminogen Activator Promotes Intracranial Aneurysm Formation","abstract":"<jats:sec>\n            <jats:title>Background and Purpose—</jats:title>\n            <jats:p>Although the mechanisms that contribute to intracranial aneurysm (IA) formation and rupture are not totally elucidated, inflammation and matrix remodeling are incriminated. Because tPA (tissue-type plasminogen activator) controls both inflammatory and matrix remodeling processes, we hypothesized that tPA could be involved in the pathophysiology of IA.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Methods—</jats:title>\n            <jats:p>Immunofluorescence analyses of tPA and its main substrate within the aneurysmal wall of murine and human samples were performed. We then compared the formation and rupture of IAs in wild-type, tPA-deficient and type 1 plasminogen activator inhibitor–deficient mice subjected to a model of elastase-induced IA. The specific contribution of vascular versus global tPA was investigated by performing hepatic hydrodynamic transfection of a cDNA encoding for tPA in tPA-deficient mice. The formation and rupture of IAs were monitored by magnetic resonance imaging tracking for 28 days.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Results—</jats:title>\n            <jats:p>Immunofluorescence revealed increased expression of tPA within the aneurysmal wall. The number of aneurysms and their symptomatic ruptures were significantly lower in tPA-deficient than in wild-type mice. Conversely, they were higher in plasminogen activator inhibitor–deficient mice. The wild-type phenotype could be restored in tPA-deficient mice by selectively increasing circulating levels of tPA via hepatic hydrodynamic transfection of a cDNA encoding for tPA.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions—</jats:title>\n            <jats:p>Altogether, this preclinical study demonstrates that the tPA present in the blood stream is a key player of the formation of IAs. Thus, tPA should be considered as a possible new target for the prevention of IAs formation and rupture.</jats:p>\n          </jats:sec>","journal":"Stroke","year":2017,"id":607696,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"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":1560492,"name":"Romain Goulay","orcid":null,"position":1,"is_corresponding":false},{"id":1560493,"name":"Sara Martinez de Lizarrondo","orcid":null,"position":2,"is_corresponding":false},{"id":1560494,"name":"Marie Hébert","orcid":null,"position":3,"is_corresponding":false},{"id":841268,"name":"Maxime Gauberti","orcid":"0000-0003-0752-7342","position":4,"is_corresponding":false},{"id":1560495,"name":"Eric Maubert","orcid":null,"position":5,"is_corresponding":false},{"id":1560496,"name":"Barbara Delaunay","orcid":null,"position":6,"is_corresponding":false},{"id":1057368,"name":"Benjamin Gory","orcid":"0000-0003-1186-3656","position":7,"is_corresponding":false},{"id":893770,"name":"Francesco Signorelli","orcid":"0000-0002-5040-1916","position":8,"is_corresponding":false},{"id":1560497,"name":"Francis Turjman","orcid":null,"position":9,"is_corresponding":false},{"id":665337,"name":"Emmanuel Touzé","orcid":"0000-0002-7254-2162","position":10,"is_corresponding":false},{"id":1560498,"name":"Patrick Courthéoux","orcid":null,"position":11,"is_corresponding":false},{"id":1056479,"name":"Denis Vivien","orcid":"0000-0002-7636-2185","position":12,"is_corresponding":false},{"id":1179440,"name":"Cyrille Orset","orcid":"0000-0002-9139-3430","position":13,"is_corresponding":false},{"id":1560491,"name":"Paul-Emile Labeyrie","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Vascular Tissue-Type Plasminogen Activator Promotes Intracranial Aneurysm Formation","abstract":"<jats:sec>\n            <jats:title>Background and Purpose—</jats:title>\n            <jats:p>Although the mechanisms that contribute to intracranial aneurysm (IA) formation and rupture are not totally elucidated, inflammation and matrix remodeling are incriminated. Because tPA (tissue-type plasminogen activator) controls both inflammatory and matrix remodeling processes, we hypothesized that tPA could be involved in the pathophysiology of IA.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Methods—</jats:title>\n            <jats:p>Immunofluorescence analyses of tPA and its main substrate within the aneurysmal wall of murine and human samples were performed. We then compared the formation and rupture of IAs in wild-type, tPA-deficient and type 1 plasminogen activator inhibitor–deficient mice subjected to a model of elastase-induced IA. The specific contribution of vascular versus global tPA was investigated by performing hepatic hydrodynamic transfection of a cDNA encoding for tPA in tPA-deficient mice. The formation and rupture of IAs were monitored by magnetic resonance imaging tracking for 28 days.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Results—</jats:title>\n            <jats:p>Immunofluorescence revealed increased expression of tPA within the aneurysmal wall. The number of aneurysms and their symptomatic ruptures were significantly lower in tPA-deficient than in wild-type mice. Conversely, they were higher in plasminogen activator inhibitor–deficient mice. The wild-type phenotype could be restored in tPA-deficient mice by selectively increasing circulating levels of tPA via hepatic hydrodynamic transfection of a cDNA encoding for tPA.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions—</jats:title>\n            <jats:p>Altogether, this preclinical study demonstrates that the tPA present in the blood stream is a key player of the formation of IAs. Thus, tPA should be considered as a possible new target for the prevention of IAs formation and rupture.</jats:p>\n          </jats:sec>","is_dataset_classified":null,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28754830","pmcid":null,"openalex_id":"https://openalex.org/W2741016297","authors":[],"funders":[],"total_grants":0,"fwci":0.6551,"citation_percentile":0.70212473,"influential_citations":0,"citation_trend":[{"year":2018,"count":2},{"year":2020,"count":2},{"year":2021,"count":4},{"year":2022,"count":5},{"year":2023,"count":1},{"year":2024,"count":6},{"year":2026,"count":1}],"oa_status":"bronze","license":"other-oa","oa_locations":[{"url":"https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.117.017305","host_type":"journal"},{"url":"https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.117.017305","host_type":"publisher"},{"url":"https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.117.017305","host_type":"publisher"},{"url":"https://doi.org/10.1161/strokeaha.117.017305","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28754830","host_type":"repository"},{"url":"http://hdl.handle.net/11586/218701","host_type":"repository"},{"url":"https://ricerca.uniba.it/bitstream/11586/218701/1/62%20Stroke17.pdf","host_type":"repository"}],"fields_of_study":["Intracranial Aneurysms: Treatment and Complications","Protease and Inhibitor Mechanisms","Barrier Structure and Function Studies","Adult","Aneurysm, Ruptured","Animals","Female","Fluorescent Antibody Technique","Humans","Immunohistochemistry","Intracranial Aneurysm","Magnetic Resonance Imaging","Mice","Mice, Knockout","Plasminogen Activator Inhibitor 1","Rupture, Spontaneous","Tissue Plasminogen Activator"],"mesh_terms":["Adult","Animals","Intracranial Aneurysm","Female","Fluorescent Antibody Technique","Humans","Immunohistochemistry","Magnetic Resonance Imaging","Tissue Plasminogen Activator","Rupture, Spontaneous","Plasminogen Activator Inhibitor 1","Aneurysm, Ruptured","Mice, Knockout","Mice"],"keywords":["Medicine","Aneurysm","Plasminogen activator","Vascular disease","T-plasminogen activator","Tissue plasminogen activator","Internal medicine","Radiology","Cardiology","Mice","Animals","Physiopathology","Intracranial aneurysm"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Peace, Justice and strong institutions"},{"sdg_number":0,"sdg_label":"Reduced inequalities"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T06:50:50.746957Z","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":[]}