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August 29, 2026Molecular Biology Reports

Trem2 regulates macrophage phenotype via the JAK2/STAT3 signaling pathway to ameliorate ventricular remodeling after acute myocardial infarction

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Why the study?

Whether Trem2 regulates macrophage polarization and improves ventricular remodeling via the JAK2/STAT3 pathway after acute myocardial infarction remains unclear.

Population

Mouse acute myocardial infarction model

Comparison

Myeloid-specific Trem2 knockout mice vs control mice, with sTREM2 supplementation and AG490 inhibition

Design

Preclinical animal and molecular study

Key result

Trem2 deficiency exacerbated ventricular remodeling and cardiac dysfunction post-AMI, whereas exogenous sTREM2 restored JAK2/STAT3 pathway activity and ameliorated cardiac function.

Authors

ZHZefeng HeJFJing FengRYRu Yan

Discussion

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Member takes

Overview

May identify Trem2 as a post-MI HF target; hypothesis-generating and requires clinical validation before any practice change.

Key Points

  • To investigate whether the Trem2-JAK2/STAT3 signaling axis modulates macrophage polarization and mitigates pathological ventricular remodeling following acute myocardial infarction.
  • Generated myeloid-specific Trem2 knockout (Mac-Trem2KO) and control mice subjected to experimental acute myocardial infarction.
  • Assessed dynamic Trem2 expression, cardiac function, infarct size, cardiomyocyte apoptosis, collagen deposition, and overall survival rates.
  • Evaluated macrophage phenotypes using GSE218002 dataset analysis and myocardial tissue assays, alongside rescue experiments using recombinant sTREM2 and the JAK2 inhibitor AG490.
  • Trem2 expression was dynamically upregulated post-infarction, peaking during the cardiac repair phase.
  • Mac-Trem2KO mice exhibited exacerbated ventricular remodeling, increased cardiac dysfunction, suppressed JAK2/STAT3 pathway activation, and a shift toward pro-inflammatory macrophages compared to controls.
  • Exogenous sTREM2 restored JAK2/STAT3 signaling and improved cardiac function, whereas pharmacologic inhibition with AG490 reversed these protective effects.

Structured PICO

P
Population
Mouse model of acute myocardial infarction evaluating myeloid-specific Trem2 knockout and sTREM2 supplementation.
I
Intervention
Myeloid-specific Trem2 knockout, exogenous sTREM2 supplementation, and AG490 (JAK2/STAT3 inhibitor) administration.
C
Comparator
Control mice.
O
Outcome
Ventricular remodeling and cardiac function.surrogate

The Trem2-JAK2/STAT3 signaling axis regulates macrophage phenotypic switching and represents a promising therapeutic target for ameliorating post-AMI myocardial remodeling.

Cite This Study

He et al. (2026) studied acute myocardial infarction. Trem2 deficiency (Mac-Trem2KO) and sTREM2 supplementation vs. Control mice was evaluated on ventricular remodeling and cardiac function. Trem2 deficiency exacerbated ventricular remodeling and cardiac dysfunction post-AMI, whereas exogenous sTREM2 restored JAK2/STAT3 pathway activity and ameliorated cardiac function.

synapsesocial.com/papers/6a92bf928e5d7d1fc0c12408https://doi.org/10.1007/s11033-026-12622-z
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Also Consider

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

  1. 1Macrophage-TREM2 promotes cardiac repair by restricting the infiltration of CD82025 · 10 citations
  2. 2TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway in mice2024 · 61 citations
  3. 3MiR-378a-3p Promotes Macrophage Polarization from M1 to M2 for Cardiac Repair after Infarction Via Trem12026
  4. 4TREM2 regulates continual efferocytosis of apoptotic neurons by monocyte-derived macrophages via AKT-PFKFB2-mediated glycolytic reprogramming after acute ischemic stroke2026
  5. 5Spatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2hi macrophages in infarcted hearts2022 · 207 citations