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Endothelial cells adopt a pro-reparative immune responsive signature during cardiac injury.

Title:	Endothelial cells adopt a pro-reparative immune responsive signature during cardiac injury.
Authors:	Long H; Interdepartmental Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, TX, USA.; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.; Steimle JD; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.; Grisanti Canozo FJ; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.; Kim JH; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.; Cardiomyocyte Renewal Laboratory, The Texas Heart Institute, Houston, TX, USA.; Li X; Cardiomyocyte Renewal Laboratory, The Texas Heart Institute, Houston, TX, USA.; Morikawa Y; Cardiomyocyte Renewal Laboratory, The Texas Heart Institute, Houston, TX, USA.; Park M; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.; Turaga D; Section of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Adachi I; Section of Cardiothoracic Surgery, Department of Surgery, Baylor College of Medicine, Houston, TX, USA.; Wythe JD; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX, USA.; Samee MAH; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.; Martin JF; Interdepartmental Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, TX, USA jfmartin@bcm.edu.; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.; Cardiomyocyte Renewal Laboratory, The Texas Heart Institute, Houston, TX, USA.; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX, USA.; Center for Organ Repair and Renewal, Baylor College of Medicine, Houston, TX, USA.
Source:	Life science alliance [Life Sci Alliance] 2023 Nov 27; Vol. 7 (2). Date of Electronic Publication: 2023 Nov 27 (Print Publication: 2024).
Publication Type:	Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Language:	English
Journal Info:	Publisher: Life Science Alliance, LLC Country of Publication: United States NLM ID: 101728869 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2575-1077 (Electronic) Linking ISSN: 25751077 NLM ISO Abbreviation: Life Sci Alliance Subsets: MEDLINE
Imprint Name(s):	Original Publication: [Woodbury, NY] : Life Science Alliance, LLC, [2018]-
MeSH Terms:	Myocardial Infarction/genetics ; Myocardial Infarction/metabolism ; Heart Failure*; Endothelial Cells/metabolism ; Signal Transduction/genetics ; Mice ; Humans ; Animals ; Child ; Heart
Abstract:	Modulation of the heart's immune microenvironment is crucial for recovery after ischemic events such as myocardial infarction (MI). Endothelial cells (ECs) can have immune regulatory functions; however, interactions between ECs and the immune environment in the heart after MI remain poorly understood. We identified an EC-specific IFN responsive and immune regulatory gene signature in adult and pediatric heart failure (HF) tissues. Single-cell transcriptomic analysis of murine hearts subjected to MI uncovered an EC population (IFN-ECs) with immunologic gene signatures similar to those in human HF. IFN-ECs were enriched in regenerative-stage mouse hearts and expressed genes encoding immune responsive transcription factors (Irf7, Batf2, and Stat1). Single-cell chromatin accessibility studies revealed an enrichment of these TF motifs at IFN-EC signature genes. Expression of immune regulatory ligand genes by IFN-ECs suggests bidirectional signaling between IFN-ECs and macrophages in regenerative-stage hearts. Our data suggest that ECs may adopt immune regulatory signatures after cardiac injury to accompany the reparative response. The presence of these signatures in human HF and murine MI models suggests a potential role for EC-mediated immune regulation in responding to stress induced by acute injury in MI and chronic adverse remodeling in HF.; (© 2023 Long et al.)
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Grant Information:	T32 HL139430 United States HL NHLBI NIH HHS; R01 HL118761 United States HL NHLBI NIH HHS; R01 HL127717 United States HL NHLBI NIH HHS; R01 HL169511 United States HL NHLBI NIH HHS; F31 HL156681 United States HL NHLBI NIH HHS; K99 HL169742 United States HL NHLBI NIH HHS; F32 HL156465 United States HL NHLBI NIH HHS
Entry Date(s):	Date Created: 20231127 Date Completed: 20231129 Latest Revision: 20241223
Update Code:	20260130
PubMed Central ID:	PMC10681909
DOI:	10.26508/lsa.202201870
PMID:	38012001
Database:	MEDLINE

Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't