Resident Cardiac Macrophages Mediate Adaptive Myocardial Remodeling
Authored by Nicole R. Wong, Jay Mohan, Benjamin J Kopecky, Shuchi Guo, Lixia Du, Jamison Leid, Oleksandr Dmytrenko, Hannah Luehmann, Geetika Bajpai, Laura Ewald, Lauren Bell, Nikhil Patel, Inessa Lokshina, Andrea Bredemeyer, Carla J. Weinheimer, Jessica M. Nigro, Attila Kovacs, Sachio Morimoto, Peter O. Bayguinov, Max. R. Fisher, James A.J. Fitzpatrick, Slava Epelman, Daniel Kreisel, Rajan Sah, Yongjian Liu, Hongzhen Hu, and Kory J. Lavine
Posted
January 30, 2021
Server
bioRxiv
Abstract
Summary Cardiac macrophages represent a heterogeneous cell population with distinct origins, dynamics, and functions. Recent studies have revealed that C-C Chemokine Receptor 2 positive (CCR2+) macrophages derived from infiltrating monocytes regulate myocardial inflammation and heart failure pathogenesis. Comparatively little is known about the functions of tissue resident (CCR2−) macrophages. Herein, we identify an essential role for CCR2− macrophages in the chronically failing heart. Depletion of CCR2− macrophages in mice with dilated cardiomyopathy accelerated mortality and impaired ventricular remodeling and coronary angiogenesis, adaptive changes necessary to maintain cardiac output in the setting of reduced cardiac contractility. Mechanistically, CCR2− macrophages interacted with neighboring cardiomyocytes via focal adhesion complexes and were activated in response to mechanical stretch through a transient receptor potential vanilloid 4 (TRPV4) dependent pathway that controlled growth factor expression. These findings establish a role for tissue resident macrophages in adaptive cardiac remodeling and introduce a new mechanism of cardiac macrophage activation.
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