Myeloid Cell-Specific Epidermal Growth Factor Receptor (EGFR) Regulates the Immune Response in the Infarcted Heart
CIRCULATION(2021)
Abstract
A mountain of evidence suggests paramount roles for myeloid cells in cardiac physiology. For one, these leukocytes have been reported to play major roles in the maintenance of functional and structural homeostasis. Additionally, following an injury, myeloid cell processes can enormously influence both short- and long-term remodeling and repair outcomes, ultimately informing heart failure. Given these significant roles, a lot of recent work has focused on examining exactly how these leukocytes might be regulated. Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that is known to critically govern cell function through for instance proliferation, migration, and survival. Interestingly, recent reports suggest that EGFR regulates macrophage activation and function, however it is currently unknown if, and how EGFR might influence myeloid cell responses within the heart. Thus, our group has generated myeloid cell-specific EGFR knockout mice (EGFRmylKO) to determine the impact of such deletion on cardiac homeostasis and post injury outcomes. We hypothesize that myeloid cell-specific EGFR is a central regulator of cardiovascular inflammation, and is key in influencing post injury outcomes. To date, we have identified that in the absence of myeloid expressed EGFR, 12-16-week-old mice exhibit increased cardiomyocyte size and “fetal gene program” transcripts when compared to both age matched floxed EGFR (EGFRf/f) and LysM cre controls. Further, we have subjected EGFRmylKOand controls to experimental myocardial infarction (MI), and have observed decreased systolic function inEGFRmylKO. To begin understanding these phenotypes, we have analyzed basal and post injury cardiacmyeloid populations. We have observed that EGFRmylKO mice exhibit increased c-c chemokine receptor type2 (CCR2+) resident macrophages, and an increase in monocytes and macrophages 1 week following MI. Altogether, these results suggest novel roles for EGFR in the failing heart.
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Key words
epidermal growth factor receptor,egfr,infarcted heart,immune response,myeloid
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