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February 6, 2026European Heart Journal

Epigenomic rewiring of the cardio-renal axis in obesity-related heart failure with preserved ejection fraction

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Why the study?

Renal dysfunction amplifies mortality in cardiometabolic HFpEF, but the role of epigenomic and transcriptional alterations in driving cardio-renal impairment remained unclear.

Population

Mouse model of cmHFpEF and control mice

Comparison

High-fat diet and L-NAME vs control diet and vehicle

Design

Preclinical animal study

Follow-up

15 weeks

Key result

In a mouse model of cmHFpEF, high-fat diet and L-NAME induced renal dysfunction and epigenomic rewiring, with BET proteins regulating pathways involved in inflammation and fibrosis.

Authors

NANatalia AtzemianSMS A MohammedHKHarikrishnan Kaipananickal

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Overview

Should not change HFpEF practice; hypothesis-generating for BET-targeted epigenomic therapies in cardio-renal impairment.

Key Points

  • This research explores the role of epigenomic and transcriptional alterations in renal impairment associated with cardiometabolic heart failure with preserved ejection fraction.
  • Utilized a mouse model of cardiometabolic heart failure with preserved ejection fraction (cmHFpEF) with a high-fat diet and L-NAME treatment.
  • Performed deep renal phenotyping including biomarker profiling, histological analysis, RNA sequencing, and proteomics.
  • Conducted CUT&RUN assays to study chromatin accessibility and BET protein distribution.
  • cmHFpEF mice exhibited significant renal dysfunction, indicated by elevated levels of creatinine, cystatin C, and galectin-3.
  • Histological analysis revealed alterations in tissue architecture, including increased collagen presence.
  • RNA sequencing and proteomics identified key signaling molecules implicated in metabolism and inflammation.
  • BET proteins showed increased binding to genes involving critical pathways such as TGF-β and PPAR-α.

Structured PICO

P
Population
Mouse model of cardiometabolic heart failure with preserved ejection fraction induced by 15 weeks of high-fat diet and L-NAME.
C
Comparator
Control mice receiving a control diet (10 kcal% fat) and vehicle in drinking water
O
Outcome
Renal biomarker profiling, histological analysis, RNA-Sequencing, Proteomics, and CUT&RUN assay for chromatin accessibility and BET protein distributionsurrogate

Epigenomic rewiring, particularly involving BET proteins, is a critical orchestrator of cardio-renal impairment in a mouse model of cardiometabolic HFpEF.

Cite This Study

Atzemian et al. (2025) studied Cardiometabolic heart failure with preserved ejection fraction (cmHFpEF). High-fat diet and L-NAME vs. Control diet (10 kcal% fat) and vehicle was evaluated on Renal dysfunction and epigenomic/transcriptional alterations. In a mouse model of cmHFpEF, high-fat diet and L-NAME induced renal dysfunction and epigenomic rewiring, with BET proteins regulating pathways involved in inflammation and fibrosis.

synapsesocial.com/papers/698585cb8f7c464f230097b3https://doi.org/10.1093/eurheartj/ehaf784.4705
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