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August 2, 2026Journal of the American Heart AssociationOpen Access

Cellular Retinoic Acid–Binding Protein 2 Promotes Ischemia‐Induced Cardiac Fibroblast Activation and Fibrosis Through Suppression of MRE11‐RAD50‐NBS1–Mediated DNA Repair

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Key result

CRABP2 knockdown in myofibroblasts preserves LV function and attenuates interstitial fibrosis in mice.

Why the study?

DNA damage and defective repair promote fibroblast activation, but the upstream regulators linking DNA damage responses to profibrotic remodeling remain unclear.

Does CRABP2 modulation affect cardiac fibroblast activation and fibrosis in models of ischemic heart failure?

Population

Human ischemic cardiomyopathy datasets, an isoproterenol-induced mouse model, and neonatal cardiac fibroblasts

Comparison

CRABP2 knockdown vs CRABP2 overexpression

Design

Preclinical in vivo, in vitro, and transcriptomic study

Authors

ZSZhenyang SuHSHui ShenJSJin‐Yu Sun

Discussion

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Member takes

Overview

CRABP2 modulation of fibroblasts may influence ischemic remodeling; leaves open therapeutic targeting pending human validation.

Key Points

  • This study aims to elucidate the role of CRABP2 in cardiac fibroblast activation and its impact on ischemic heart failure.
  • Analyzed single-cell RNA sequencing data from human ischemic cardiomyopathy to identify fibroblast genes.
  • Utilized mouse models with CRABP2 knockdown and overexpression to assess ventricular function and fibrosis.
  • Conducted in vitro experiments on neonatal cardiac fibroblasts under TGF-β stimulation and CRABP2 modulation.
  • Single-cell analyses revealed CRABP2 upregulation in profibrotic fibroblast subsets.
  • In vivo CRABP2 knockdown preserved left ventricular function and reduced interstitial fibrosis; CRABP2 overexpression worsened these conditions.
  • CRABP2 promoted TGF-β–induced fibroblast activation and collagen production by inhibiting MRN-mediated DNA repair.

Structured PICO

Does CRABP2 modulation affect cardiac fibroblast activation and fibrosis in models of ischemic heart failure?

P
Population
Single-cell RNA sequencing data sets from human ischemic cardiomyopathy; in vivo isoproterenol-induced mouse model; in vitro neonatal cardiac fibroblasts.
I
Intervention
CRABP2 knockdown or overexpression using Postn promoter-driven adeno-associated viruses (in vivo) and gain or loss of function with TGF-β stimulation (in vitro).
C
Comparator
Control (implied, not explicitly stated in abstract).
O
Outcome
Ventricular function and fibrosis (in vivo); fibroblast migration, proliferation, activation, and collagen production (in vitro).surrogate

CRABP2 drives profibrotic cardiac fibroblast activation by inhibiting MRE11/MRN-mediated DNA repair, identifying the CRABP2-MRE11-MRN axis as a potential therapeutic target for limiting fibrotic remodeling in ischemic heart failure.

Cite This Study

Su et al. (2026) studied Ischemic heart failure and cardiac fibrosis. CRABP2 knockdown or overexpression was evaluated on Ventricular function and fibrosis. CRABP2 knockdown in myofibroblasts preserved left ventricular function and attenuated interstitial fibrosis, whereas its overexpression exacerbated dysfunction and fibrosis in mice.

synapsesocial.com/papers/6a6eeb201b0468a7eeab412ahttps://doi.org/10.1161/jaha.126.049049
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1CRABP1 protects the heart from isoproterenol-induced acute and chronic remodeling2018 · 52 citations
  2. 2Maf1 Ameliorates Cardiac Fibrosis by Methylation of the Sfrp2 Promoter Through Dnmt12026
  3. 3Trbp inhibits cardiac fibrosis through TGF-β pathway-mediated cross-talk between cardiomyocytes and fibroblasts2025 · 4 citations
  4. 4Inhibition of Mitofusin-2 Promotes Cardiac Fibroblast Activation via the PERK/ATF4 Pathway and Reactive Oxygen Species2019 · 35 citations
  5. 5Restoration of RBM22 overcomes the transcriptional and epigenetic barriers of cardiomyocyte proliferation for heart regeneration2026