Immune cells in repair of the infarcted myocardium

Chen, Bijun; Frangogiannis, Nikolaos G.

doi:10.1111/micc.12305

Cited by 73 publications

(55 citation statements)

References 125 publications

(121 reference statements)

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“…For many years, it was assumed that cardiac myocytes must be the primary target of therapeutic interventions after ischemia, but more recent data showed that inflammation substantially drives the remodeling process and affects scar size. 32,33 Therefore, modulation of the inflammatory processes as shown here can be considered a further interesting strategy to ameliorate cardiac remodeling after AMI. In this context, myeloid cells have gained much attention besides their role in driving myocardial inflammation.…”

Section: Discussionmentioning

confidence: 93%

IGF1 Treatment Improves Cardiac Remodeling after Infarction by Targeting Myeloid Cells

et al. 2019

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Section: Discussionmentioning

confidence: 93%

IGF1 Treatment Improves Cardiac Remodeling after Infarction by Targeting Myeloid Cells

et al. 2019

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“…Infarct wound healing is a complex process that involves a coordinated cascade of sequential cellular events. During the proliferative phase, fibroblasts phenotypically differentiate to myofibroblasts that are responsible for producing the extracellular matrix in the wound microenvironment (31). Macrophages provide regulatory factors and mediators that orchestrate the phenotypic and functional changes of fibroblasts, and critically regulate the synthesis and organization of collagen deposition in wound healing (32,33).…”

Section: Discussionmentioning

confidence: 99%

The glucocorticoid receptor in monocyte‐derived macrophages is critical for cardiac infarct repair and remodeling

et al. 2017

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Cell- and tissue-specific actions of glucocorticoids are mediated by the glucocorticoid receptor. Here, we demonstrate that the glucocorticoid receptor (GR) in macrophages is essential for cardiac healing after myocardial infarction. Compared with GRflox (wild-type controls), GRLysMCre mice that lacked GR in myeloid cells showed increased acute mortality as a result of cardiac rupture. Seven days after left coronary artery ligation, GRLysMCre mice exhibited worse cardiac function and adverse remodeling associated with impaired scar formation and angiogenic response to ischemic injury. Inactivation of GR altered the functional differentiation/maturation of monocyte-derived macrophages in the infarcted myocardium. Mechanistically, CD45+/CD11b+/Ly6G−/F4/80+ macrophages isolated from GRLysMCre infarcts showed deregulation of factors that control inflammation, neovascularization, collagen degradation, and scar tissue formation. Moreover, we demonstrate that cardiac fibroblasts sorted from the ischemic myocardium of GRLysMCre mice compared with cells isolated from injured GRflox hearts displayed higher matrix metalloproteinase 2 expression, and we provide evidence that the macrophage GR regulates myofibroblast differentiation in the infarct microenvironment during the early phase of wound healing. In summary, GR signaling in macrophages, playing a crucial role in tissue-repairing mechanisms, could be a potential therapeutic target during wound healing after ischemic myocardial injury.—Galuppo, P., Vettorazzi, S., Hövelmann, J., Scholz, C.-J., Tuckermann, J. P., Bauersachs, J., Fraccarollo, D. The glucocorticoid receptor in monocyte-derived macrophages is critical for cardiac infarct repair and remodeling.

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“…10 Multiple different immune cells are recruited to the ventricular myocardium following ischaemic injury in adult mammals. 11,12 Macrophages play critical roles in tissue repair and scarring, but recent reports have suggested a, somewhat contradictory, role for macrophage subsets in complete regeneration of the neonatal mouse heart. 13,14 Indeed, macrophage depletion at different time-points post-injury in a model of liver fibrosis can have dramatically different effects on fibrosis/scarring vs. regeneration.…”

Section: Introductionmentioning

confidence: 99%

Specific macrophage populations promote both cardiac scar deposition and subsequent resolution in adult zebrafish

Bevan

Lim

Venkatesh

et al. 2019

Cardiovascular Research

161

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Aims A robust inflammatory response to tissue injury is a necessary part of the repair process but the deposition of scar tissue is a direct downstream consequence of this response in many tissues including the heart. Adult zebrafish not only possess the capacity to regenerate lost cardiomyocytes but also to remodel and resolve an extracellular scar within tissues such as the heart, but this scar resolution process remains poorly understood. This study aims to characterize the scarring and inflammatory responses to cardiac damage in adult zebrafish in full and investigate the role of different inflammatory subsets specifically in scarring and scar removal. Methods and results Using stable transgenic lines, whole organ imaging and genetic and pharmacological interventions, we demonstrate that multiple inflammatory cell lineages respond to cardiac injury in adult zebrafish. In particular, macrophage subsets (tnfα+ and tnfα−) play prominent roles with manipulation of different phenotypes suggesting that pro-inflammatory (tnfα+) macrophages promote scar deposition following cardiac injury whereas tnfα− macrophages facilitate scar removal during regeneration. Detailed analysis of these specific macrophage subsets reveals crucial roles for Csf1ra in promoting pro-inflammatory macrophage-mediated scar deposition. Additionally, the multifunctional cytokine Osteopontin (Opn) (spp1) is important for initial scar deposition but also for resolution of the inflammatory response and in late-stage ventricular collagen remodelling. Conclusions This study demonstrates the importance of a correctly balanced inflammatory response to facilitate scar deposition during repair but also to allow subsequent scar resolution, and full cardiac regeneration, to occur. We have identified Opn as having both pro-fibrotic but also potentially pro-regenerative roles in the adult zebrafish heart, driving Collagen deposition but also controlling inflammatory cell resolution.

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Immune cells in repair of the infarcted myocardium

Cited by 73 publications

References 125 publications

IGF1 Treatment Improves Cardiac Remodeling after Infarction by Targeting Myeloid Cells

IGF1 Treatment Improves Cardiac Remodeling after Infarction by Targeting Myeloid Cells

The glucocorticoid receptor in monocyte‐derived macrophages is critical for cardiac infarct repair and remodeling

Specific macrophage populations promote both cardiac scar deposition and subsequent resolution in adult zebrafish

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