Journal article
Hypoxia sensing in resident cardiac macrophages regulates monocyte fate specification following ischemic heart injury
Nature cardiovascular research, Vol.3(11), pp.1337-1355
11/01/2024
DOI: 10.1038/s44161-024-00553-6
PMID: 39433910
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 macrophages resulted in arrested progression through this trajectory and accumulation of an inflammatory intermediate state marked by persistent Arg1 expression. Depletion of the Arg1
trajectory accelerated cardiac remodeling following ischemic injury. Our findings unveil distinct trajectories of monocyte differentiation and identify hypoxia sensing as an important determinant of monocyte differentiation following myocardial infarction.
Details
- Title: Subtitle
- Hypoxia sensing in resident cardiac macrophages regulates monocyte fate specification following ischemic heart injury
- Creators
- Farid F Kadyrov - Washington University in St. LouisAndrew L Koenig - Washington University in St. LouisJunedh M Amrute - Washington University in St. LouisHao Dun - Washington University in St. LouisWenjun Li - Washington University in St. LouisCarla J Weinheimer - Washington University in St. LouisJessica M Nigro - Washington University in St. LouisAttila Kovacs - Washington University in St. LouisAndrea L Bredemeyer - Washington University in St. LouisSteven Yang - Washington University in St. LouisShibali Das - Washington University in St. LouisVinay R Penna - Washington University in St. LouisAlekhya Parvathaneni - Washington University in St. LouisLulu Lai - Washington University in St. LouisNiklas Hartmann - Washington University in St. LouisBenjamin J Kopecky - Washington University in St. LouisDaniel Kreisel - Washington University in St. LouisKory J Lavine - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Nature cardiovascular research, Vol.3(11), pp.1337-1355
- DOI
- 10.1038/s44161-024-00553-6
- PMID
- 39433910
- ISSN
- 2731-0590
- eISSN
- 2731-0590
- Grant note
- T32 GM007067 / NIGMS NIH HHS S10 OD028597 / NIH HHS R01 HL139714 / NHLBI NIH HHS T32 HL134635 / NHLBI NIH HHS R35 HL161185 / NHLBI NIH HHS P30 CA091842 / NCI NIH HHS R01 HL151078 / NHLBI NIH HHS R01 HL138466 / NHLBI NIH HHS P30 AR073752 / NIAMS NIH HHS T32 GM007200 / NIGMS NIH HHS
- Language
- English
- Date published
- 11/01/2024
- Academic Unit
- Stead Family Department of Pediatrics
- Record Identifier
- 9985161354402771
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