Myeloid cell-specific deletion of epidermal growth factor receptor aggravates acute cardiac injury

Myeloid cells, including macrophages, play important roles as first responders to cardiac injury and stress. Epidermal growth factor receptor (EGFR) has been identified as a mediator of macrophage responsiveness to select diseases, though its impact on cardiac function or remodeling following acute...

Full description

Saved in:

Bibliographic Details
Published in:	Clinical science (1979) Vol. 137; no. 19; p. 1513
Main Authors:	Okyere, Ama D, Nayak, Tapas K, Patwa, Viren, Teplitsky, David, McEachern, Erin, Carter, Rhonda L, Xu, Heli, Gao, Erhe, Zhou, Yan, Tilley, Douglas G
Format:	Journal Article
Language:	English
Published:	England 11-10-2023
Subjects:	Animals ErbB Receptors - genetics ErbB Receptors - metabolism Heart Macrophages - metabolism Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Myeloid Cells - metabolism Myocardial Infarction - metabolism Ventricular Remodeling - genetics myeloid cell macrophages epidermal growth factor receptor myocardial remodeling
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Myeloid cells, including macrophages, play important roles as first responders to cardiac injury and stress. Epidermal growth factor receptor (EGFR) has been identified as a mediator of macrophage responsiveness to select diseases, though its impact on cardiac function or remodeling following acute ischemic injury is unknown. We aimed to define the role of myeloid cell-specific EGFR in the regulation of cardiac function and remodeling following acute myocardial infarction (MI)-induced injury. Floxed EGFR mice were bred with homozygous LysM-Cre (LMC) transgenic mice to yield myeloid-specific EGFR knockout (mKO) mice. Via echocardiography, immunohistochemistry, RNA sequencing and flow cytometry, the impact of myeloid cell-specific EGFR deletion on cardiac structure and function was assessed at baseline and following injury. Compared with LMC controls, myeloid cell-specific EGFR deletion led to an increase in cardiomyocyte hypertrophy at baseline. Bulk RNASeq analysis of isolated cardiac Cd11b+ myeloid cells revealed substantial changes in mKO cell transcripts at baseline, particularly in relation to predicted decreases in neovascularization. In response to myocardial infarction, mKO mice experienced a hastened decline in cardiac function with isolated cardiac Cd11b+ myeloid cells expressing decreased levels of the pro-reparative mediators Vegfa and Il10, which coincided with enhanced cardiac hypertrophy and decreased capillary density. Overall, loss of EGFR qualitatively alters cardiac resident macrophages that promotes a low level of basal stress and a more rapid decrease in cardiac function along with worsened repair following acute ischemic injury.
ISSN:	1470-8736
DOI:	10.1042/CS20230804