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September 4, 2023Nature Cardiovascular ResearchOpen Access

Cell-intrinsic effects of clonal hematopoiesis in heart failure

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Why the study?

Whether enhanced inflammatory signatures in heart failure patients with CHIP derive from mutant cells or reflect systemic pro-inflammatory activation is unclear.

What are the cell-intrinsic effects of CHIP mutant cells in patients with heart failure?

Population

Patients with heart failure

Comparison

CHIP mutant cells vs wild-type cells

Design

Single-cell sequencing study

Key result

DNMT3A mutant monocytes, CD4+ T cells, and NK cells from heart failure patients exhibited significantly increased expression of genes associated with inflammation and effector functions compared to wild-type cells.

Authors

WAWesley AbplanalpBSBianca SchuhmacherSCSebastian Cremer

Discussion

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Overview

Cell-intrinsic CHIP effects may drive HF inflammation; leaves open whether targeting mutant clones improves outcomes.

Study Design

Type

Observational (n=6)

Structured PICO

What are the cell-intrinsic effects of CHIP mutant cells in patients with heart failure?

P
Population
6 male patients averaging 66 years of age with stable chronic heart failure and previous myocardial infarction, known to have DNMT3A clonal hematopoiesis mutations.
E
Exposure
Single-cell sequencing (MutDetect-Seq) to assess cell-intrinsic effects of CHIP mutant cells
C
Comparator
Wild-type cells (monocytes and T cells)
O
Outcome
Gene expression profiles and cellular activation signatures (inflammation, phagocytosis, effector functions)surrogate

CHIP mutations in heart failure patients intrinsically alter immune cell gene expression, promoting inflammation and potentially explaining the worse prognosis associated with CHIP.

Limitations

  • Small sample size of 6 patients
  • All patients were male
  • Limited statistical power for in-depth analysis of divergent T cell populations

Cite This Study

Abplanalp et al. (2023) conducted an observational in Heart failure with DNMT3A clonal hematopoiesis (n=6). DNMT3A mutation vs. Wild-type cells was evaluated on Differential gene expression in circulating immune cells. DNMT3A mutant monocytes, CD4+ T cells, and NK cells from heart failure patients exhibited significantly increased expression of genes associated with inflammation and effector functions compared to wild-type cells.

synapsesocial.com/papers/6a6598e3fbf3afd72ce90226https://doi.org/10.1038/s44161-023-00322-x
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