Left Ventricular T-Cell Recruitment Contributes to the Pathogenesis of Heart Failure
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- Tania Nevers
- From the Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (T.N., A.M.S., A.G.-P., A.K., F.V., M.A., N.K.K., R.H.K., R.M.B., P.A.); and the Program in Immunology, Sackler School for Graduate Studies, Department of Medicine, Tufts University School of Medicine, Boston, MA (F.V., R.H.K., P.A.).
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- Ane M. Salvador
- From the Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (T.N., A.M.S., A.G.-P., A.K., F.V., M.A., N.K.K., R.H.K., R.M.B., P.A.); and the Program in Immunology, Sackler School for Graduate Studies, Department of Medicine, Tufts University School of Medicine, Boston, MA (F.V., R.H.K., P.A.).
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- Anna Grodecki-Pena
- From the Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (T.N., A.M.S., A.G.-P., A.K., F.V., M.A., N.K.K., R.H.K., R.M.B., P.A.); and the Program in Immunology, Sackler School for Graduate Studies, Department of Medicine, Tufts University School of Medicine, Boston, MA (F.V., R.H.K., P.A.).
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- Andrew Knapp
- From the Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (T.N., A.M.S., A.G.-P., A.K., F.V., M.A., N.K.K., R.H.K., R.M.B., P.A.); and the Program in Immunology, Sackler School for Graduate Studies, Department of Medicine, Tufts University School of Medicine, Boston, MA (F.V., R.H.K., P.A.).
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- Francisco Velázquez
- From the Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (T.N., A.M.S., A.G.-P., A.K., F.V., M.A., N.K.K., R.H.K., R.M.B., P.A.); and the Program in Immunology, Sackler School for Graduate Studies, Department of Medicine, Tufts University School of Medicine, Boston, MA (F.V., R.H.K., P.A.).
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- Mark Aronovitz
- From the Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (T.N., A.M.S., A.G.-P., A.K., F.V., M.A., N.K.K., R.H.K., R.M.B., P.A.); and the Program in Immunology, Sackler School for Graduate Studies, Department of Medicine, Tufts University School of Medicine, Boston, MA (F.V., R.H.K., P.A.).
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- Navin K. Kapur
- From the Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (T.N., A.M.S., A.G.-P., A.K., F.V., M.A., N.K.K., R.H.K., R.M.B., P.A.); and the Program in Immunology, Sackler School for Graduate Studies, Department of Medicine, Tufts University School of Medicine, Boston, MA (F.V., R.H.K., P.A.).
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- Richard H. Karas
- From the Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (T.N., A.M.S., A.G.-P., A.K., F.V., M.A., N.K.K., R.H.K., R.M.B., P.A.); and the Program in Immunology, Sackler School for Graduate Studies, Department of Medicine, Tufts University School of Medicine, Boston, MA (F.V., R.H.K., P.A.).
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- Robert M. Blanton
- From the Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (T.N., A.M.S., A.G.-P., A.K., F.V., M.A., N.K.K., R.H.K., R.M.B., P.A.); and the Program in Immunology, Sackler School for Graduate Studies, Department of Medicine, Tufts University School of Medicine, Boston, MA (F.V., R.H.K., P.A.).
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- Pilar Alcaide
- From the Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (T.N., A.M.S., A.G.-P., A.K., F.V., M.A., N.K.K., R.H.K., R.M.B., P.A.); and the Program in Immunology, Sackler School for Graduate Studies, Department of Medicine, Tufts University School of Medicine, Boston, MA (F.V., R.H.K., P.A.).
Description
<jats:sec> <jats:title>Background—</jats:title> <jats:p>Despite the emerging association between heart failure (HF) and inflammation, the role of T cells, major players in chronic inflammation, has only recently begun to be explored. Whether T-cell recruitment to the left ventricle (LV) participates in the development of HF requires further investigation to identify novel mechanisms that may serve for the design of alternative therapeutic interventions.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> Real-time videomicroscopy of T cells from nonischemic HF patients or from mice with HF induced by transverse aortic constriction revealed enhanced adhesion to activated vascular endothelial cells under flow conditions in vitro compared with T cells from healthy subjects or sham mice. T cells in the mediastinal lymph nodes and the intramyocardial endothelium were both activated in response to transverse aortic constriction and the kinetics of LV T-cell infiltration was directly associated with the development of systolic dysfunction. In response to transverse aortic constriction, T cell–deficient mice (T-cell receptor, TCRα <jats:sup>−/−</jats:sup> ) had preserved LV systolic and diastolic function, reduced LV fibrosis, hypertrophy and inflammation, and improved survival compared with wild-type mice. Furthermore, T-cell depletion in wild-type mice after transverse aortic constriction prevented HF. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>T cells are major contributors to nonischemic HF. Their activation combined with the activation of the LV endothelium results in LV T-cell infiltration negatively contributing to HF progression through mechanisms involving cytokine release and induction of cardiac fibrosis and hypertrophy. Reduction of T-cell infiltration is thus identified as a novel translational target in HF.</jats:p> </jats:sec>
Journal
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- Circulation: Heart Failure
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Circulation: Heart Failure 8 (4), 776-787, 2015-07
Ovid Technologies (Wolters Kluwer Health)
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Details 詳細情報について
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- CRID
- 1363951796171830144
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- ISSN
- 19413297
- 19413289
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- Data Source
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- Crossref