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dc.contributor.authorSager, Hendrik B.
dc.contributor.authorHulsmans, Maarten
dc.contributor.authorLavine, Kory J.
dc.contributor.authorMoreira, Marina B.
dc.contributor.authorHeidt, Timo
dc.contributor.authorCourties, Gabriel P
dc.contributor.authorSun, Yuan
dc.contributor.authorIwamoto, Yoshiko
dc.contributor.authorTricot, Benoit
dc.contributor.authorKhan, Omar F.
dc.contributor.authorDahlman, James E.
dc.contributor.authorBorodovsky, Anna
dc.contributor.authorFitzgerald, Kevin
dc.contributor.authorAnderson, Daniel Griffith
dc.contributor.authorWeissleder, Ralph
dc.contributor.authorLibby, Peter
dc.contributor.authorSwirski, Filip K.
dc.contributor.authorNahrendorf, Matthias
dc.date.accessioned2016-10-05T15:16:04Z
dc.date.issued2016
dc.identifier.citationSager, Hendrik B., Maarten Hulsmans, Kory J. Lavine, Marina B. Moreira, Timo Heidt, Gabriel Courties, Yuan Sun, et al. 2016. “Proliferation and Recruitment Contribute to Myocardial Macrophage Expansion in Chronic Heart FailureNovelty and Significance.” Circulation Research 119 (7) (July 21): 853–864. doi:10.1161/circresaha.116.309001.en_US
dc.identifier.issn0009-7330en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:28979888
dc.description.abstractRationale: Macrophages reside in the healthy myocardium, participate in ischemic heart disease, and modulate myocardial infarction (MI) healing. Their origin and roles in post-MI remodeling of nonischemic remote myocardium, however, remain unclear. Objective: This study investigated the number, origin, phenotype, and function of remote cardiac macrophages residing in the nonischemic myocardium in mice with chronic heart failure after coronary ligation. Methods and Results: Eight weeks post MI, fate mapping and flow cytometry revealed that a 2.9-fold increase in remote macrophages results from both increased local macrophage proliferation and monocyte recruitment. Heart failure produced by extensive MI, through activation of the sympathetic nervous system, expanded medullary and extramedullary hematopoiesis. Circulating Ly6Chigh monocytes rose from 64±5 to 108±9 per microliter of blood (P<0.05). Cardiac monocyte recruitment declined in Ccr2−/− mice, reducing macrophage numbers in the failing myocardium. Mechanical strain of primary murine and human macrophage cultures promoted cell cycle entry, suggesting that the increased wall tension in post-MI heart failure stimulates local macrophage proliferation. Strained cells activated the mitogen-activated protein kinase pathway, whereas specific inhibitors of this pathway reduced macrophage proliferation in strained cell cultures and in the failing myocardium (P<0.05). Steady-state cardiac macrophages, monocyte-derived macrophages, and locally sourced macrophages isolated from failing myocardium expressed different genes in a pattern distinct from the M1/M2 macrophage polarization paradigm. In vivo silencing of endothelial cell adhesion molecules curbed post-MI monocyte recruitment to the remote myocardium and preserved ejection fraction (27.4±2.4 versus 19.1±2%; P<0.05). Conclusions: Myocardial failure is influenced by an altered myeloid cell repertoire.en_US
dc.language.isoen_USen_US
dc.publisherOvid Technologies (Wolters Kluwer Health)en_US
dc.relation.isversionofdoi:10.1161/CIRCRESAHA.116.309001en_US
dash.licenseMETA_ONLY
dc.titleProliferation and Recruitment Contribute to Myocardial Macrophage Expansion in Chronic Heart Failureen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalCirculation Researchen_US
dash.depositing.authorLibby, Peter
dash.embargo.until10000-01-01
dc.identifier.doi10.1161/CIRCRESAHA.116.309001*
dash.authorsorderedfalse
dash.contributor.affiliatedAnderson, Daniel
dash.contributor.affiliatedCourties, Gabriel
dash.contributor.affiliatedHulsmans, Maarten
dash.contributor.affiliatedSwirski, Filip
dash.contributor.affiliatedNahrendorf, Matthias
dash.contributor.affiliatedLibby, Peter
dash.contributor.affiliatedWeissleder, Ralph


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