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FASEB J. 2013 Mar;27(3):871-81. doi: 10.1096/fj.12-214049. Epub 2012 Nov 16.

Monocytes/macrophages prevent healing defects and left ventricular thrombus formation after myocardial infarction.

Author information

1
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

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.

PMID:
23159933
DOI:
10.1096/fj.12-214049
[Indexed for MEDLINE]

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