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Immunity. 2019 Jul 16;51(1):131-140.e5. doi: 10.1016/j.immuni.2019.06.010.

Gata6+ Pericardial Cavity Macrophages Relocate to the Injured Heart and Prevent Cardiac Fibrosis.

Author information

1
Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, T2N 1N4, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, T2N 1N4, Canada.
2
Section of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Libin Cardiovascular Institute of Alberta, Calgary, AB, T2N 1N4, Canada.
3
Molecular Immunology and Inflammation Branch, NIAMS, NIH, Rockville, MD 20892, USA.
4
Biodata Mining and Discovery Section, NIAMS, Rockville, MD, 20892, USA.
5
Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
6
Department of Surgery, Universitätsklinikum Erlangen, Friedrich-Alexander Universität, Erlangen-Nürnberg, 91054, Germany.
7
Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, T2N 1N4, Canada; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, T2N 1N4, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, T2N 1N4, Canada. Electronic address: pkubes@ucalgary.ca.

Abstract

Macrophages play an important role in structural cardiac remodeling and the transition to heart failure following myocardial infarction (MI). Previous research has focused on the impact of blood-derived monocytes on cardiac repair. Here we examined the contribution of resident cavity macrophages located in the pericardial space adjacent to the site of injury. We found that disruption of the pericardial cavity accelerated maladaptive post-MI cardiac remodeling. Gata6+ macrophages in mouse pericardial fluid contributed to the reparative immune response. Following experimental MI, these macrophages invaded the epicardium and lost Gata6 expression but continued to perform anti-fibrotic functions. Loss of this specialized macrophage population enhanced interstitial fibrosis after ischemic injury. Gata6+ macrophages were present in human pericardial fluid, supporting the notion that this reparative function is relevant in human disease. Our findings uncover an immune cardioprotective role for the pericardial tissue compartment and argue for the reevaluation of surgical procedures that remove the pericardium.

KEYWORDS:

Pericardial macrophage; fibrosis; myocardial infarction

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