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February 6, 2026European Heart Journal

Myeloid NCOR1 deletion prevents diastolic dysfunction and reduces myocardial inflammation in HFpEF mice.

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Why the study?

Inflammatory response is a key player in HFpEF, but the underlying mechanisms driving myocardial macrophage inflammation and pathological remodeling are poorly understood.

Does myeloid cell-specific NCOR1 deletion prevent macrophage inflammation and cardiac dysfunction in HFpEF?

Population

LV specimens from HFpEF patients and control donors, murine HFpEF models, and macrophage cell lines

Comparison

Myeloid-specific NCOR1 knockout vs control in HFpEF models and HFpEF vs controls

Design

Translational and preclinical study using human tissue, mouse models, and in vitro assays

Key result

Macrophage NCOR1 deletion in HFpEF mice prevented diastolic dysfunction, lung congestion, and exercise intolerance, and reduced myocardial inflammation.

Authors

EGEra GoricaLVLudovica Di VenanzioIPI Papadopoulou

Discussion

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Member takes

Overview

Supports NCOR1 as macrophage target in HFpEF; hypothesis-generating, should not yet change practice.

Key Points

  • This research investigates how nuclear receptor co-repressor 1 (NCOR1) influences macrophage inflammation in heart failure with preserved ejection fraction (HFpEF).
  • Used FACS analysis and single nuclei RNA-seq for immune cell profiling in human and murine HFpEF hearts.
  • Conducted in vitro experiments with RAW-264.7 cells under metabolic stress and bone marrow-derived macrophages from HFpEF mice.
  • Induced HFpEF in mice via high-fat diet and hemodynamic stress, then analyzed cardiac function through ultrasound imaging.
  • Generated myeloid cell-specific NCOR1 knockout transgenic mice to explore NCOR1's role in HFpEF.
  • Expansion of macrophage populations and increased NCOR1 expression in HFpEF hearts observed through snRNA-seq.
  • NCOR1 deletion in HFpEF mice reduced inflammation, improved diastolic function, and mitigated exercise intolerance.
  • In vitro, NCOR1 upregulation was linked to metabolic stress, activating the NLRP3-IL1b pathway, while its depletion prevented macrophage inflammation.

Structured PICO

Does myeloid cell-specific NCOR1 deletion prevent macrophage inflammation and cardiac dysfunction in HFpEF?

P
Population
Human left ventricular specimens from HFpEF patients and control donors; murine HFpEF models (high-fat diet + L-NAME); RAW-264.7 cells; bone marrow-derived macrophages.
I
Intervention
Myeloid cell-specific NCOR1 deletion (Ncor1-KO) and in vitro NCOR1 depletion.
C
Comparator
Wild-type mice with HFpEF; age-matched control human donors; control macrophages.
O
Outcome
Diastolic dysfunction (E/e' ratio, IVRT), lung congestion, exercise tolerance, and myocardial inflammation.surrogate

NCOR1 is a key driver of macrophage inflammation in HFpEF, and its targeted deletion prevents diastolic dysfunction and exercise intolerance in preclinical models.

Cite This Study

Gorica et al. (2025) studied Heart failure with preserved ejection fraction (HFpEF). Macrophage NCOR1 deletion vs. Control (wild-type/non-depleted) was evaluated on Diastolic dysfunction, lung congestion, exercise intolerance, and myocardial inflammation. Macrophage NCOR1 deletion in HFpEF mice prevented diastolic dysfunction, lung congestion, and exercise intolerance, and reduced myocardial inflammation.

synapsesocial.com/papers/698585bd8f7c464f2300952ahttps://doi.org/10.1093/eurheartj/ehaf784.4664
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