Key result
Exogenous sTREM2 improves post-AMI cardiac function and remodeling by restoring JAK2/STAT3 pathway activity.
Why the study?
Whether Trem2 regulates macrophage polarization and improves ventricular remodeling via the JAK2/STAT3 pathway after acute myocardial infarction remains unclear.
The Trem2-JAK2/STAT3 signaling axis regulates macrophage phenotypic switching and represents a promising therapeutic target for ameliorating post-AMI myocardial remodeling.
Answers are grounded in this paper and cite their sources.
May identify Trem2 as a post-MI HF target; hypothesis-generating and requires clinical validation before any practice change.
BACKGROUND: Pathological ventricular remodeling after acute myocardial infarction (AMI) is a critical pathological basis of heart failure, with macrophages as the core driver of inflammatory imbalance. Trem2-expressing macrophages regulate inflammation resolution and tissue repair, and the JAK2/STAT3 pathway is involved in macrophage phenotype modulation. However, whether Trem2 regulates macrophage polarization and improves ventricular remodeling via this pathway post-AMI remains unclear. This study aimed to explore the regulatory role of the Trem2-JAK2/STAT3 axis in macrophage polarization and ventricular remodeling after AMI. METHODS: Dynamic Trem2 expression was detected in a mouse AMI model. Myeloid-specific Trem2 knockout mice (Mac-Trem2KO) were generated, and cardiac function, infarct size, cardiomyocyte apoptosis, collagen deposition and survival rate were compared between knockout and control groups. The GSE218002 dataset and myocardial tissues were used to verify the effect of Trem2 deficiency on macrophage phenotypes. sTREM2 supplementation and AG490 inhibition were performed to verify the JAK2/STAT3 pathway-mediated regulatory mechanism. RESULTS: Trem2 expression was upregulated after AMI and peaked at the repair phase. Compared with controls, Mac-Trem2KO mice showed more severe ventricular remodeling and cardiac dysfunction. Trem2 deficiency suppressed JAK2/STAT3 pathway activation and skewed macrophages toward a pro-inflammatory phenotype. Exogenous sTREM2 restored pathway activity and ameliorated cardiac function, while AG490 recapitulated the cardiac dysfunction induced by Trem2 deficiency. CONCLUSION: Trem2 mediates macrophage phenotypic switching by activating the JAK2/STAT3 pathway in macrophages, thus inhibiting pathological ventricular remodeling. The Trem2-JAK2/STAT3 signaling axis represents a promising therapeutic target for post-AMI myocardial remodeling.
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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.
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