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Go toJCI InsightAboutEditorsConsulting EditorsFor authorsAlertsAdvertiseSubscribeContactCurrent IssuePast IssuesBy specialtyCardiologyGastroenterologyImmunologyMetabolismNephrologyNeuroscienceOncologyPulmonologyVascular biologyAll...VideosConversations with Giants in MedicineAuthor's TakesReviewsReviewsView all reviews...Review SeriesMetabolism and Inflammation (Jan 2017)Hypoxia and Inflammation (Oct 2016)Extracellular Vesicles (Apr 2016)HIV (Feb 2016)Cancer Immunotherapy (Sep 2015)Autoimmunity (Jun 2015)Enteric Nervous System (Mar 2015)View all review series...CollectionsRecently publishedCommentariesEditorialsOpinionScientific Show StoppersTop read articlesClinical MedicineJCI This MonthCurrent issuePast issuesThe Journal of Clinical InvestigationAboutEditorsConsulting EditorsFor authorsCurrent issuePast issuesBy specialtySubscribeAlertsAdvertiseContactVideosConversations with Giants in MedicineAuthor's TakesCollectionsRecently publishedBrief ReportsTechnical AdvancesCommentariesEditorialsHindsightReview seriesReviewsThe Attending PhysicianFirst Author PerspectivesScientific Show StoppersTop read articlesRecently published- MoreCardiac myofibroblast engulfment of dead cells facilitates recovery after myocardial infarctionMyocardial infarction (MI) results in the generation of dead cells in the infarcted area. These cells are swiftly removed by phagocytes to minimize inflammation and limit expansion of the damaged...Published January 3, 2017Categories:Research ArticleCardiologyInflammationCardiac myofibroblast engulfment of dead cells facilitates recovery after myocardial infarctionTextPDFAbstractMyocardial infarction (MI) results in the generation of dead cells in the infarcted area. These cells are swiftly removed by phagocytes to minimize inflammation and limit expansion of the damaged area. However, the types of cells and molecules responsible for the engulfment of dead cells in the infarcted area remain largely unknown. In this study, we demonstrated that cardiac myofibroblasts, which execute tissue fibrosis by producing extracellular matrix proteins, efficiently engulf dead cells. Furthermore, we identified a population of cardiac myofibroblasts that appears in the heart after MI in humans and mice. We found that these cardiac myofibroblasts secrete milk fat globule-epidermal growth factor 8 (MFG-E8), which promotes apoptotic engulfment, and determined that serum response factor is important for MFG-E8 production in myofibroblasts. Following MFG-E8–mediated engulfment of apoptotic cells, myofibroblasts acquired antiinflammatory properties. MFG-E8 deficiency in mice led to the accumulation of unengulfed dead cells after MI, resulting in exacerbated inflammatory responses and a substantial decrease in survival. Moreover, MFG-E8 administration into infarcted hearts restored cardiac function and morphology. MFG-E8–producing myofibroblasts mainly originated from resident cardiac fibroblasts and cells that underwent endothelial-mesenchy
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