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September 14, 2026Journal of Cellular and Molecular MedicineOpen Access

Higher Mf1 macrophage proportions strongly correlate with increased neutrophil NETosis in HF.

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Population

26 patients, including those with heart failure due to dilated, ischemic, or inflammatory cardiomyopathy…

Design

Case-control

Key result

In patients with heart failure, the proportion of Mf1 macrophages was significantly positively correlated with the proportion of neutrophils undergoing NETosis (r = +0.79, p < 0.01).

Authors

SKSawa KostinHCHéctor A. Cabrera-FuentesMRManfred Richter

Discussion

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Overview

Association warrants no clinical action in heart failure; leaves open mechanistic role and therapeutic targeting of Mf1-NETosis.

Key Points

  • To evaluate the relationship between neutrophil NETosis and macrophage activation phenotypes within the myocardium of patients with diverse forms of heart failure.
  • Examined ventricular biopsies from patients with heart failure due to dilated (n = 7), ischemic (n = 7), or inflammatory (n = 7) cardiomyopathy, as well as 5 control subjects.
  • Quantified NETosis using CD66b+/citrullinated histone 3+/myeloperoxidase+ neutrophils, along with CD66b+/TNF-α+ (Mf1) and CD66b+/CD206+ (Mf2) macrophage subsets via histological analysis.
  • Neutrophil NETosis rates were 49.4% [IQR, 45–52] in inflammatory, 45.3% [39–46] in ischemic, and 41.5% [37–45] in dilated cardiomyopathy, compared to 4% [3.8–4.2] in controls.
  • Proinflammatory Mf1 macrophage proportions were significantly higher in inflammatory (78.5% [70–85]), dilated (53.1% [48.4–54.4]), and ischemic cardiomyopathy (54.5% [51–60]) than in controls (3% [1.6–5.5]; p < 0.01 for controls vs all heart failure groups).
  • Proinflammatory Mf1 macrophages positively correlated with the extent of NETosis (r = +0.79, p < 0.01), whereas anti-inflammatory Mf2 macrophages showed no significant correlation (r = −0.12, p = 0.28).

Study Design

Type

Observational (n=26)

Structured PICO

P
Population
26 patients, including 21 with heart failure (dilated, ischemic, or inflammatory cardiomyopathy) and 5 controls, who provided ventricular biopsies.
C
Comparator
Control patients (n=5)
O
Outcome
Proportion of neutrophils undergoing NETosis and proportion of Mf1/Mf2 macrophages in ventricular biopsiessurrogate

Main Result

Effect estimate: r = +0.79

p-value: p=<0.01

In patients with heart failure, increased neutrophil NETosis in the myocardium is strongly correlated with the activation of macrophages toward a proinflammatory Mf1 phenotype.

Cite This Study

Kostin et al. (2026) conducted an observational in Heart failure (n=26). Heart failure vs. Control patients was evaluated on Correlation between Mf1 macrophages and the proportion of NETosis (r = +0.79, p=<0.01). In patients with heart failure, the proportion of Mf1 macrophages was significantly positively correlated with the proportion of neutrophils undergoing NETosis (r = +0.79, p < 0.01).

synapsesocial.com/papers/6aa7afef79e9260bc85aac75https://doi.org/10.1111/jcmm.71306
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Also Consider

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

  1. 1NETosis is an important component of chronic inflammation in patients with heart failure2024 · 1 citations
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  3. 3NEUTROPHILS ARE INDISPENSABLE FOR ADVERSE CARDIAC REMODELING IN HEART FAILURE2023 · 3 citations
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  5. 5Neutrophil Extracellular Traps in Myocardial Tissue Drive Cardiac Dysfunction and Adverse Outcomes in Patients With Heart Failure With Dilated Cardiomyopathy2024 · 40 citations