Journal article
Epicardial YAP/TAZ orchestrate an immunosuppressive response following myocardial infarction
The Journal of clinical investigation, v 127(3), pp 899-911
01 Mar 2017
PMID: 28165342
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Ischemic heart disease resulting from myocardial infarction (MI) is the most prevalent form of heart disease in the United States. Post-MI cardiac remodeling is a multifaceted process that includes activation of fibroblasts and a complex immune response. T-regulatory cells (Tregs), a subset of CD4(+) T cells, have been shown to suppress the innate and adaptive immune response and limit deleterious remodeling following myocardial injury. However, the mechanisms by which injured myocardium recruits suppressive immune cells remain largely unknown. Here, we have shown a role for Hippo signaling in the epicardium in suppressing the post-infarct inflammatory response through recruitment of Tregs. Mice deficient in epicardial YAP and TAZ, two core Hippo pathway effectors, developed profound post-MI pericardial inflammation and myocardial fibrosis, resulting in cardiomyopathy and death. Mutant mice exhibited fewer suppressive Tregs in the injured myocardium and decreased expression of the gene encoding IFN-., a known Treg inducer. Furthermore, controlled local delivery of IFN-. following MI rescued Treg infiltration into the injured myocardium of YAP/TAZ mutants and decreased fibrosis. Collectively, these results suggest that epicardial Hippo signaling plays a key role in adaptive immune regulation during the post-MI recovery phase.
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Details
- Title
- Epicardial YAP/TAZ orchestrate an immunosuppressive response following myocardial infarction
- Creators
- Vimal Ramjee - Univ Penn, Penn Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USADeqiang Li - Univ Penn, Penn Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USALauren J. Manderfield - Univ Penn, Penn Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USAFeiyan Liu - Univ Penn, Penn Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USAKurt A. Engleka - Univ Penn, Penn Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USAHaig Aghajanian - Univ Penn, Penn Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USAChristopher B. Rodell - Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAWen Lu - Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USAVivienne Ho - Univ Penn, Penn Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USATao Wang - Univ Penn, Penn Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USALi Li - Univ Penn, Penn Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USAAnamika Singh - Duke NUS Med Sch Singapore, Cardiovasc & Metab Disorders Program, Singapore, SingaporeDasan M. Cibi - Duke NUS Med Sch Singapore, Cardiovasc & Metab Disorders Program, Singapore, SingaporeJason A. Burdick - Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USAManvendra K. Singh - Duke NUS Med Sch Singapore, Cardiovasc & Metab Disorders Program, Singapore, SingaporeRajan Jain - Univ Penn, Penn Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USAJonathan A. Epstein - Univ Penn, Penn Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USA
- Publication Details
- The Journal of clinical investigation, v 127(3), pp 899-911
- Publisher
- Amer Soc Clinical Investigation Inc
- Number of pages
- 13
- Grant note
- Predoctoral Fellowship Award from the American Heart Association WW Smith Endowed Chair U01 HL100405; K08 HL119553 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Cotswold Foundation T32 / Division of Cardiology of the University of Pennsylvania NRF-NRFF2016-01 / Singapore National Research Foundation; National Research Foundation, Singapore U01HL100405 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Established Investigator Award from the American Heart Association; American Heart Association Burroughs Wellcome Fund
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000396658300018
- Scopus ID
- 2-s2.0-85015852852
- Other Identifier
- 991019176643104721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Medicine, Research & Experimental