T cell costimulation blockade blunts pressure overload-induced heart failure
| العنوان: | T cell costimulation blockade blunts pressure overload-induced heart failure |
|---|---|
| المؤلفون: | Gianluigi Condorelli, Federica Riva, Roberto Papait, Tomas Stølen, Elisa Di Pasquale, Debora Vignali, Marinos Kallikourdis, Daniele Catalucci, Claudia Sardi, Leonardo Elia, Giuliana Roselli, Anne Marie Ormbostad Berre, Giuseppe Faggian, Pierluigi Carullo, Andrea Fumero, Carolina M. Greco, Elisa Martini, Cristiano Rumio |
| المصدر: | Web of Science Nature Communications Nature Communications, Vol 8, Iss 1, Pp 1-14 (2017) |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Genetics and Molecular Biology (all), TCell, T-Lymphocytes, medicine.medical_treatment, General Physics and Astronomy, heart failure, 030204 cardiovascular system & hematology, Biochemistry, 0302 clinical medicine, FOLLICULAR HELPER, SYSTEMIC-LUPUS-ERYTHEMATOSUS, Cells, Cultured, IN-VIVO, Mice, Knockout, Multidisciplinary, Chemistry (all), MURINE MODEL, Interleukin-10, 3. Good health, Interleukin 10, Cytokine, costimulation, Rheumatoid arthritis, SYSTEMIC-LUPUS-ERYTHEMATOSUS, MYOCARDIAL-INFARCTION, MURINE MODEL, DILATED CARDIOMYOPATHY, RHEUMATOID-ARTHRITIS, FOLLICULAR HELPER, SELF-TOLERANCE, FAILING HEART, STEADY-STATE, IN-VIVO, medicine.symptom, Immunosuppressive Agents, medicine.drug, musculoskeletal diseases, STEADY-STATE, Science, TCell, costimulation, heart failure, Cardiomegaly, Inflammation, Article, General Biochemistry, Genetics and Molecular Biology, Abatacept, SELF-TOLERANCE, 03 medical and health sciences, Physics and Astronomy (all), Pressure, medicine, Animals, Humans, FAILING HEART, Pressure overload, business.industry, Macrophages, General Chemistry, medicine.disease, DILATED CARDIOMYOPATHY, Blockade, RHEUMATOID-ARTHRITIS, Mice, Inbred C57BL, 030104 developmental biology, Animals, Newborn, MYOCARDIAL-INFARCTION, Heart failure, Immunology, Cancer research, Biochemistry, Genetics and Molecular Biology (all), business |
| الوصف: | Heart failure (HF) is a leading cause of mortality. Inflammation is implicated in HF, yet clinical trials targeting pro-inflammatory cytokines in HF were unsuccessful, possibly due to redundant functions of individual cytokines. Searching for better cardiac inflammation targets, here we link T cells with HF development in a mouse model of pathological cardiac hypertrophy and in human HF patients. T cell costimulation blockade, through FDA-approved rheumatoid arthritis drug abatacept, leads to highly significant delay in progression and decreased severity of cardiac dysfunction in the mouse HF model. The therapeutic effect occurs via inhibition of activation and cardiac infiltration of T cells and macrophages, leading to reduced cardiomyocyte death. Abatacept treatment also induces production of anti-inflammatory cytokine interleukin-10 (IL-10). IL-10-deficient mice are refractive to treatment, while protection could be rescued by transfer of IL-10-sufficient B cells. These results suggest that T cell costimulation blockade might be therapeutically exploited to treat HF. Abatacept is an FDA-approved drug used for treatment of rheumatoid arthritis. Here the authors show that abatacept reduces cardiomyocyte death in a mouse model of heart failure by inhibiting activation and heart infiltration of T cells and macrophages, an effect mediated by IL-10, suggesting a potential therapy for heart failure. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f386111f783e04812013dc8f91b2ebc4Test http://hdl.handle.net/11562/971509Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f386111f783e04812013dc8f91b2ebc4 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |