Vascular Tissue-Type Plasminogen Activator Promotes Intracranial Aneurysm Formation
| العنوان: | Vascular Tissue-Type Plasminogen Activator Promotes Intracranial Aneurysm Formation |
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| المؤلفون: | Francis Turjman, Barbara Delaunay, Sara Martinez de Lizarrondo, Benjamin Gory, Emmanuel Touzé, Marie Hébert, Maxime Gauberti, Francesco Signorelli, Patrick Courtheoux, Cyrille Orset, Romain Goulay, Eric Maubert, Denis Vivien, Paul-Emile Labeyrie |
| المصدر: | Stroke. 48:2574-2582 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adult, 0301 basic medicine, Pathology, medicine.medical_specialty, Fluorescent Antibody Technique, Inflammation, Aneurysm, Ruptured, Immunofluorescence, Tissue plasminogen activator, Mice, 03 medical and health sciences, 0302 clinical medicine, Plasminogen Activator Inhibitor 1, medicine, Animals, Humans, Vascular tissue, Mice, Knockout, Advanced and Specialized Nursing, Rupture, Spontaneous, integumentary system, medicine.diagnostic_test, business.industry, Intracranial Aneurysm, Transfection, Immunohistochemistry, Magnetic Resonance Imaging, Phenotype, Pathophysiology, 030104 developmental biology, Tissue Plasminogen Activator, Female, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, Plasminogen activator, 030217 neurology & neurosurgery, medicine.drug |
| الوصف: | Background and Purpose— 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. Methods— 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. Results— 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. Conclusions— 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. |
| تدمد: | 1524-4628 0039-2499 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b3ac8435e70e027466518cd3077d675dTest https://doi.org/10.1161/strokeaha.117.017305Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b3ac8435e70e027466518cd3077d675d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244628 00392499 |
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