Hypoxia sensing in resident cardiac macrophages regulates monocyte fate specification following ischemic heart injury.

ABSTRACT: Myocardial infarction initiates cardiac remodeling and is central to heart failure pathogenesis. Following myocardial ischemia-reperfusion injury, monocytes enter the heart and differentiate into diverse subpopulations of macrophages. Here we show that deletion of Hif1α, a hypoxia response transcription factor, in resident cardiac macrophages led to increased remodeling and overrepresentation of macrophages expressing arginase 1 (Arg1). Arg1⁺ macrophages displayed an inflammatory gene signature and may represent an intermediate state of monocyte differentiation. Lineage tracing of Arg1⁺ macrophages revealed a monocyte differentiation trajectory consisting of multiple transcriptionally distinct states. We further showed that deletion of Hif1α in resident cardiac macrop

SUBMITTER: Kadyrov FF 

PROVIDER: S-EPMC12696718 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature