Work

Metabolic and Signaling Pathways of Macrophage Reprogramming in Atherosclerosis and Myocardial Infarction

Year: 2026

Type: article

Abstract: Atherosclerosis and myocardial infarction remain the predominant contributors to mortality despite advances in interventional cardiology. Chronic inflammatory responses mediated by macrophages serve as a critical determinant of the pathogenesis of cardiovascular diseases. This review systematically dissects the immunometabolic and signaling networks underlying macrophage reprogramming, with a focus on key cardiovascular diseases. We assess the characteristics of M1 macrophages, which involve aerobic glycolysis, activation of the pentose phosphate pathway, and disruption of the tricarboxylic acid cycle, compared to M2 macrophages that rely on oxidative phosphorylation and fatty acid oxidation. Integrated signaling pathways dynamically regulate these metabolic programmes—centred on TLR/NF-κB-mediated inflammatory priming, JAK/STAT-dependent transcriptional polarization, and PI3K/Akt/mTOR-AMPK-PPARγ metabolic checkpoints, which interpret microenvironmental signals to control macrophage polarization. Within atherosclerotic lesions, we demonstrate that M1-dominant macrophage populations exacerbate plaque inflammation and compromise structural integrity, whereas M2 macrophages augment inflammatory resolution and tissue restoration. Following myocardial infarction, the timely therapeutic reprogramming from M1 to M2 phenotype is essential for efficiently attenuating adverse cardiac remodeling and improving cardiac function. Targeting metabolic enzymes and signaling pathways offers a promising strategy for reprogramming macrophages and mitigating cardiovascular diseases. Addresses species-specific differences in human vs murine immunometabolism. Emphasizes the context‑dependent roles of signaling pathways in macrophage polarization. Discusses the spatiotemporal dynamics of macrophage subsets in CVDs. Proposes precision macrophage reprogramming strategies with therapeutic timing.

Source: Inflammation

DOI: 10.1007/s10753-026-02542-2

Authors: Zhanyuan Ding, Yilin Wang, Shengsong Chen, Lingling Yu

Institutions: Nanchang University, Second Affiliated Hospital of Nanchang University, China-Japan Friendship Hospital, First Affiliated Hospital of Jiangxi Medical College

Language: English

Topic: Atherosclerosis and Cardiovascular Diseases

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,790