title: Monocytes/macrophages prevent healing defects and left ventricular thrombus formation after myocardial infarction.
abstract: Myocardial infarction (MI) leads to rapid necrosis of cardiac myocytes. To achieve tissue integrity and function, inflammatory cells are activated, including monocytes/macrophages. However, the effect of monocyte/macrophage recruitment after MI remains poorly defined. After experimental MI, monocytes and macrophages were depleted through serial injections of clodronate-containing liposomes. Monocyte/macrophage infiltration was reduced in the myocardium after MI by active treatment. Mortality was increased due to thromboembolic events in monocyte- and macrophage-depleted animals (92 vs. 33%; P<0.01). Left ventricular thrombi were detectable as early as 24 h after MI; this was reproduced in a genetic model of monocyte/macrophage ablation. A general prothrombotic state, increased infarct expansion, and deficient neovascularization were not observed. Severely compromised extracellular matrix remodeling (collagen I, placebo liposome vs. clodronate liposome, 2.4 ± 0.2 vs. 0.8 ± 0.2 arbitrary units; P<0.001) and locally lost integrity of the endocardium after MI are potential mechanisms. Patients with a left ventricular thrombus had a relative decrease of CD14CD16 monocyte/macrophage subsets in the peripheral blood after MI (no thrombus vs. thrombus, 14.2 ± 0.9 vs. 7.80 ± 0.4%; P<0.05). In summary, monocytes/macrophages are of central importance for healing after MI. Impaired monocyte/macrophage function appears to be an unrecognized new pathophysiological mechanism for left ventricular thrombus development after MI.
authors.affiliation: Department of Internal Medicine I, University Hospital Würzburg, Comprehensive Heart Failure Center, University of Würzburg, Oberdürrbacher Straße 6, 97080 Würzburg, Germany. frantz_s@medizin.uni-wuerzburg.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Frantz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hofmann
authors.forename: Daniela
authors.initials: D
authors.lastname: Fraccarollo
authors.forename: Andreas
authors.initials: A
authors.lastname: Schäfer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kranepuhl
authors.forename: Ina
authors.initials: I
authors.lastname: Hagedorn
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Helga
authors.initials: H
authors.lastname: Wagner
authors.forename: Barbara
authors.initials: B
authors.lastname: Bayer
authors.forename: Christina
authors.initials: C
authors.lastname: Pachel
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schön
authors.forename: Susanne
authors.initials: S
authors.lastname: Kneitz
authors.forename: Tobias
authors.initials: T
authors.lastname: Bobinger
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D004002:Clodronic Acid / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018950:Lipopolysaccharide Receptors; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D017452:Receptors, IgG; D013927:Thrombosis / Q000378:metabolism* / Q000473:pathology
chemical_list: D050071:Bone Density Conservation Agents; C485700:Fcgr3 protein, mouse; D018950:Lipopolysaccharide Receptors; D008081:Liposomes; D017452:Receptors, IgG; D004002:Clodronic Acid