دورية أكاديمية
Cytotoxic CD8+ T cells promote granzyme B-dependent adverse post-ischemic cardiac remodeling.
| العنوان: | Cytotoxic CD8+ T cells promote granzyme B-dependent adverse post-ischemic cardiac remodeling. |
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| المؤلفون: | Santos-Zas, Icia, Lemarié, Jeremie, Zlatanova, Ivana, Cachanado, Marine, Seghezzi, Jean-Christophe, Benamer, Hakim, Goube, Pascal, Vandestienne, Marie, Cohen, Raphael, Ezzo, Maya, Duval, Vincent, Zhang, Yujiao, Su, Jin-Bo, Bizé, Alain, Sambin, Lucien, Bonnin, Philippe, Branchereau, Maxime, Heymes, Christophe, Tanchot, Corinne, Vilar, José, Delacroix, Clement, Hulot, Jean-Sebastien, Cochain, Clement, Bruneval, Patrick, Danchin, Nicolas, Tedgui, Alain, Mallat, Ziad, Simon, Tabassome, Ghaleh, Bijan, Silvestre, Jean-Sébastien, Ait-Oufella, Hafid |
| بيانات النشر: | Springer Science and Business Media LLC //dx.doi.org/10.1038/s41467-021-21737-9 Nat Commun |
| سنة النشر: | 2021 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Animals, Apoptosis, CD8-Positive T-Lymphocytes, Disease Models, Animal, Female, Granzymes, Heart, Heart Failure, Homeodomain Proteins, Humans, Male, Mice, Inbred C57BL, Knockout, Myocardial Infarction, Myocardium, Swine, Transcriptome, Ventricular Remodeling |
| الوصف: | Acute myocardial infarction is a common condition responsible for heart failure and sudden death. Here, we show that following acute myocardial infarction in mice, CD8+ T lymphocytes are recruited and activated in the ischemic heart tissue and release Granzyme B, leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardial function. Depletion of CD8+ T lymphocytes decreases apoptosis within the ischemic myocardium, hampers inflammatory response, limits myocardial injury and improves heart function. These effects are recapitulated in mice with Granzyme B-deficient CD8+ T cells. The protective effect of CD8 depletion on heart function is confirmed by using a model of ischemia/reperfusion in pigs. Finally, we reveal that elevated circulating levels of GRANZYME B in patients with acute myocardial infarction predict increased risk of death at 1-year follow-up. Our work unravels a deleterious role of CD8+ T lymphocytes following acute ischemia, and suggests potential therapeutic strategies targeting pathogenic CD8+ T lymphocytes in the setting of acute myocardial infarction. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Electronic; application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/318861Test |
| DOI: | 10.17863/CAM.65976 |
| الإتاحة: | https://doi.org/10.17863/CAM.65976Test https://www.repository.cam.ac.uk/handle/1810/318861Test |
| حقوق: | All rights reserved |
| رقم الانضمام: | edsbas.CA37E9E |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.65976 |
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