Macrophages Facilitate Electrical Conduction in the Heart

Maarten Hulsmans; Sebastian Clauss; Ling Xiao; Aaron D. Aguirre; Kevin R. King; Alan Hanley; William J. Hucker; Eike M. Wülfers; Gunnar Seemann; Gabriel Courties; Yoshiko Iwamoto; Yuan Sun; Andrej J. Savol; Hendrik B. Sager; Kory J. Lavine; Gregory A. Fishbein; Diane E. Capen; Nicolas Da Silva; Lucile Miquerol; Hiroko Wakimoto; Christine E. Seidman; Jonathan G. Seidman; Ruslan I. Sadreyev; Kamila Naxerova; Richard N. Mitchell; Dennis Brown; Peter Libby; Ralph Weissleder; Filip K. Swirski; Peter Kohl; Claudio Vinegoni; David J. Milan; Patrick T. Ellinor; Matthias Nahrendorf

doi:10.1016/j.cell.2017.03.050

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Macrophages Facilitate Electrical Conduction in the Heart

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Macrophages Facilitate Electrical Conduction in the Heart

Maarten Hulsmans, Sebastian Clauss, Ling Xiao, Aaron D. Aguirre, Kevin R. King, Alan Hanley, William J. Hucker, Eike M. Wülfers, Gunnar Seemann, Gabriel Courties, …

Cell, Vol.169(3), pp.510-522.e20

20/04/2017

DOI: https://doi.org/10.1016/j.cell.2017.03.050

PMID: 28431249

Résumé

atrioventricular node

computational modeling

connexin 43

electrical conduction

gap junctions

heart

macrophages

optogenetics

single-cell RNA-sequencing

tissue clearing

Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11bDTR mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction. [Display omitted] •Tissue-resident macrophages abound in the mouse and human AV nodes•Connexin 43 connects macrophages with cardiomyocytes•Macrophages modulate the electrical activity of cardiomyocytes•Macrophages assist normal AV nodal conduction Heart-resident macrophages directly modulate the electrical properties of cardiomyocytes.

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Titre: Macrophages Facilitate Electrical Conduction in the Heart
Créateurs - sans rôle: Maarten Hulsmans - Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Sebastian Clauss - Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Ling Xiao - Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Aaron D. Aguirre - Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Kevin R. King - Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Alan Hanley - Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
William J. Hucker - Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Eike M. Wülfers - Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg, Bad Krozingen, 79110 Freiburg, Germany
Gunnar Seemann - Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg, Bad Krozingen, 79110 Freiburg, Germany
Gabriel Courties - Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Yoshiko Iwamoto - Harvard Medical School
Yuan Sun - Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Andrej J. Savol - Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Hendrik B. Sager - Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Kory J. Lavine - Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MO 63110, USA
Gregory A. Fishbein - Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Diane E. Capen - Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Nicolas Da Silva - Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Lucile Miquerol - Aix Marseille University, CNRS, IBDM, 13288 Marseille, France
Hiroko Wakimoto - Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Christine E. Seidman - Brigham and Women's Hospital
Jonathan G. Seidman - Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Ruslan I. Sadreyev - Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Kamila Naxerova - Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Richard N. Mitchell - Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Dennis Brown - Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Peter Libby - Brigham and Women's Hospital
Ralph Weissleder - Harvard Medical School
Filip K. Swirski - Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Peter Kohl - Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg, Bad Krozingen, 79110 Freiburg, Germany
Claudio Vinegoni - Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
David J. Milan - Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Patrick T. Ellinor - Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Matthias Nahrendorf - Harvard Medical School
Détails de publication: Cell, Vol.169(3), pp.510-522.e20
Éditeur: Elsevier Inc
Identifiants: 99141380509311
Unité académique: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Langue: English
Type de ressource: Journal article