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February 6, 2026European Heart Journal

Modeling cardioinflammatory TET2 CHIP in engineered cardiac ventricular tissue reveals therapeutics for disease resolution

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Key result

Lanatoside C reduces TET2-KD myeloid infiltration, cardiomyocyte apoptosis, and fibrosis in a preclinical SCO model.

Why the study?

Genome-wide association studies link CVD with CHIP, particularly TET2 mutations, prompting the need to determine whether self-organizing cardiac organoids can model cardiovascular CHIP and identify potential therapeutics.

Do selected drugs like Lanatoside C reduce inflammation and improve cardiac function in a TET2 cardiac-CHIP organoid model?

Population

Self-organizing cardiac organoids infiltrated with TET2-knockdown myeloid cells

Comparison

Selected drug treatments vs vehicle/drug control groups

Design

Pre-clinical in vitro engineered cardiac organoid study

Authors

YWYue WangJKJ A Y A Krishnan

Discussion

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Member takes

Overview

Should not change practice; extends TET2 organoid models for testing repurposed agents in CHIP.

Key Points

  • The aim is to investigate the TET2 mutation's role in cardiovascular disease using engineered cardiac organoids.
  • Generated self-organizing cardiac organoids as a model for TET2 mutant CHIP.
  • Performed TET2 knockdown in myeloid cells within these organoids.
  • Conducted immunofluorescence and qPCR to assess cell infiltration and tissue damage.
  • Analyzed calcium flux to measure cardiac contractility.
  • Used RNA sequencing to evaluate transcriptional changes post drug treatment.
  • Increased inflammation and fibrosis were observed in TET2 knockdown organoids.
  • Apoptosis of cardiomyocytes was evidenced by elevated cleaved Caspase-3 and cTNT release.
  • Selected drugs reduced myeloid cell proliferation and inflammatory cytokines levels.
  • Drug-treated models exhibited improved cardiac function, showing higher frequency and amplitude of heartbeat.
  • RNA sequencing results confirmed the effectiveness of the drug candidates.

Structured PICO

Do selected drugs like Lanatoside C reduce inflammation and improve cardiac function in a TET2 cardiac-CHIP organoid model?

P
Population
Self-organizing cardiac organoids (SCO) infiltrated with TET2-knockdown myeloid cells (TET2 cardiac-CHIP model)
I
Intervention
Drug candidates including Lanatoside C
C
Comparator
Vehicle/drug control groups
O
Outcome
Inflammation, fibrosis, cardiomyocyte apoptosis, cTNT release, and cardiac contractile frequency and amplitudesurrogate

A novel TET2 cardiac-CHIP organoid model demonstrates that Lanatoside C can rescue CHIP-induced cardiac inflammation, fibrosis, and apoptosis, highlighting its potential for repurposing in CHIP-related cardiovascular disease.

Cite This Study

Wang et al. (2025) studied TET2-mutant cardiovascular CHIP. Lanatoside C vs. Vehicle was evaluated on Inflammation, fibrosis, apoptosis, and cardiac contractile function. Treatment with Lanatoside C reduced myeloid cell infiltration, inflammation, fibrosis, and cardiomyocyte apoptosis in a self-organizing cardiac organoid model of TET2-mutant CHIP.

synapsesocial.com/papers/698586ad8f7c464f2300a695https://doi.org/10.1093/eurheartj/ehaf784.4825
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Also Consider

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

  1. 1Generation of a homozygous TET2 knock-out hiPSC line for modeling of cardiovascular diseases associated with clonal hematopoiesis of indeterminate potential (CHIP)2026 · 1 citations
  2. 2Monocyte-endothelial interactions as a targetable node in clonal hematopoiesis-mediated cardiovascular disease2025
  3. 3Monocyte-endothelial interactions as a targetable node in clonal hematopoiesis-mediated cardiovascular disease2025 · 1 citations
  4. 4Accelerated adverse cardiac remodeling in a model of TET2 mutation-driven clonal hematopoiesis is ameliorated by IFNa treatment by modulating the monocyte response2025
  5. 5Clonal haematopoiesis of indeterminate potential and mortality in coronary artery disease2025 · 24 citations