Defining cardiac functional recovery in end-stage heart failure at single-cell resolution.
Journal
Nature cardiovascular research
ISSN: 2731-0590
Titre abrégé: Nat Cardiovasc Res
Pays: England
ID NLM: 9918284280206676
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
medline:
16
8
2023
pubmed:
16
8
2023
entrez:
16
8
2023
Statut:
ppublish
Résumé
Recovery of cardiac function is the holy grail of heart failure therapy yet is infrequently observed and remains poorly understood. In this study, we performed single-nucleus RNA sequencing from patients with heart failure who recovered left ventricular systolic function after left ventricular assist device implantation, patients who did not recover and non-diseased donors. We identified cell-specific transcriptional signatures of recovery, most prominently in macrophages and fibroblasts. Within these cell types, inflammatory signatures were negative predictors of recovery, and downregulation of RUNX1 was associated with recovery. In silico perturbation of RUNX1 in macrophages and fibroblasts recapitulated the transcriptional state of recovery. Cardiac recovery mediated by BET inhibition in mice led to decreased macrophage and fibroblast Runx1 expression and diminished chromatin accessibility within a Runx1 intronic peak and acquisition of human recovery signatures. These findings suggest that cardiac recovery is a unique biological state and identify RUNX1 as a possible therapeutic target to facilitate cardiac recovery.
Identifiants
pubmed: 37583573
doi: 10.1038/s44161-023-00260-8
pmc: PMC10426763
mid: NIHMS1915768
doi:
Types de publication
Journal Article
Langues
eng
Pagination
399-416Subventions
Organisme : NIAMS NIH HHS
ID : P30 AR073752
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135121
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151078
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139714
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151924
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK052574
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL161185
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL156667
Pays : United States
Organisme : CSRD VA
ID : I01 CX002291
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA091842
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL125241
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL138466
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL132067
Pays : United States
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing interests.
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