Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair
Tamar Harel-Adar,Tamar Ben Mordechai,Yoram Amsalem,Micha S. Feinberg,Jonathan Leor,Smadar Cohen +5 more
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TLDR
A new strategy for the modulation of cardiac macrophages to a reparative state, at a predetermined time after myocardial infarction (MI), in aim to promote resolution of inflammation and elicit infarct repair is investigated.Abstract:
Herein we investigated a new strategy for the modulation of cardiac macrophages to a reparative state, at a predetermined time after myocardial infarction (MI), in aim to promote resolution of inflammation and elicit infarct repair. The strategy employed intravenous injections of phosphatidylserine (PS)-presenting liposomes, mimicking the anti-inflammatory effects of apoptotic cells. Following PS-liposome uptake by macrophages in vitro and in vivo, the cells secreted high levels of anti-inflammatory cytokines [transforming growth factor β (TGFβ) and interleukin 10 (IL-10)] and upregulated the expression of the mannose receptor—CD206, concomitant with downregulation of proinflammatory markers, such as tumor necrosis factor α (TNFα) and the surface marker CD86. In a rat model of acute MI, targeting of PS-presenting liposomes to infarct macrophages after injection via the femoral vein was demonstrated by magnetic resonance imaging (MRI). The treatment promoted angiogenesis, the preservation of small scars, and prevented ventricular dilatation and remodeling. This strategy represents a unique and accessible approach for myocardial infarct repair.read more
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Macrophages in Injured Skeletal Muscle: A Perpetuum Mobile Causing and Limiting Fibrosis, Prompting or Restricting Resolution and Regeneration
TL;DR: The beneficial versus the detrimental actions of macrophages during the response to muscle injury are considered, with attention to the available information on the molecular code macrophage rely on to guide, throughout the various phases of muscle healing, the function of conventional and unconventional stem cells.
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A comparison of electrospun polymers reveals poly(3-hydroxybutyrate) fiber as a superior scaffold for cardiac repair.
CastellanoDelia,BlanesMaría,MarcoBruno,CerradaInmaculada,Ruiz-SauríAmparo,PelachoBeatriz,ArañaMiriam,A MonteroJose,CambraVicente,ProsperFelipe,SepúlvedaPilar +10 more
TL;DR: Results showed that cell adhesion and growth of mesenchymal stem cells, cardiomyocytes, and cardiac fibroblasts in vitro was dependent on the polymer substrate, with PHB and PCL polymers permitting the greatest adhesion/growth of cells.
Journal ArticleDOI
Novel therapeutic strategies for cardioprotection.
Joost P.G. Sluijter,Gianluigi Condorelli,Sean M. Davidson,Felix B. Engel,Péter Ferdinandy,Derek J. Hausenloy,Sandrine Lecour,Rosalinda Madonna,Michel Ovize,Marisol Ruiz-Meana,Rainer Schulz,Linda W. van Laake +11 more
TL;DR: Promising therapeutic strategies for cardioprotection include novel aspects of mitochondrial function, epigenetics, circadian clocks, the immune system, microvesicles, growth factors, stem cell therapy and gene therapy.
Journal ArticleDOI
Macrophages and Cardiovascular Health
TL;DR: Signals that regulate macrophages supply and function, imaging applications that can detect changes in cell numbers and phenotype, and opportunities to modulate cardiovascular inflammation by targeting macrophage biology are highlighted.
Journal ArticleDOI
IL-4 as a Repurposed Biological Drug for Myocardial Infarction through Augmentation of Reparative Cardiac Macrophages: Proof-of-Concept Data in Mice.
Yusuke Shintani,Yusuke Shintani,Tomoya Ito,Laura Fields,Manabu Shiraishi,Yuki Ichihara,Nobuhiko Sato,Mihai-Nicolae Podaru,Satoshi Kainuma,Hiroyuki Tanaka,Ken Suzuki +10 more
TL;DR: Proof-of-concept of efficacy of IL-4 treatment for acute myocardial infarction is presented, encouraging its further development.
References
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Journal Article
Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages.
Valerie A. Fadok,Dennis R. Voelker,Priscilla A. Campbell,J. John Cohen,D L Bratton,Peter M. Henson +5 more
TL;DR: The data suggest that macrophages specifically recognize phosphatidylserine that is exposed on the surface of lymphocytes during the development of apoptosis, and suggest that apoptotic lymphocytes lose membrane phospholipid asymmetry and expose phosphorus on the outer leaflet of the plasma membrane.
Journal ArticleDOI
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Journal ArticleDOI
The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions
Matthias Nahrendorf,Filip K. Swirski,Elena Aikawa,Lars Stangenberg,Thomas Wurdinger,Jose-Luiz Figueiredo,Peter Libby,Peter Libby,Ralph Weissleder,Mikael J. Pittet +9 more
TL;DR: This work identifies two distinct phases of monocyte participation after MI and proposes a model that reconciles the divergent properties of these cells in healing and identifies new therapeutic targets that can influence healing and ventricular remodeling after MI.
Journal ArticleDOI
Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-β1 secretion and the resolution of inflammation
TL;DR: In vivo that direct instillation of apoptotic cells enhanced the resolution of acute inflammation, and apoptotic cell recognition and clearance, via exposure of PS and ligation of its receptor, induce TGF-beta1 secretion, resulting in accelerated resolution of inflammation.
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