Research progress on the molecular mechanisms and targeted interventions of macrophage-mediated myocardial fibrosis

doi:10.3969/j.issn.1674-8115.2026.03.009

Abstract

Abstract:

Myocardial fibrosis is a critical pathological basis underlying the progression of various cardiovascular diseases. It is characterized by the activation of fibroblasts into myofibroblasts and excessive synthesis of collagen, leading to abnormal accumulation of the extracellular matrix, which ultimately impairs cardiac structure and function. Cardiac macrophages, as key immune cells in the cardiovascular system, exhibit diverse functions that are regulated by their origin and local microenvironment. Distinct macrophage phenotypes play different roles during myocardial injury. Pro-inflammatory macrophages mediate the early inflammatory response, whereas pro-reparative macrophages promote fibroblast activation and collagen deposition via paracrine signaling. Recent advances in high-throughput techniques, such as single-cell and spatial transcriptomics, have provided unprecedented resolution for understanding the heterogeneity, dynamic changes, and intercellular communication networks of cardiac macrophages. Conventional therapies have limited capacity in reversing established fibrosis, but emerging approaches such as nanoparticle-based delivery systems and engineered cell therapies hold promise for the precise reprogramming of cardiac macrophages. This review summarizes the heterogeneity of cardiac macrophages, highlights the molecular mechanisms by which they regulate myocardial fibrosis under pathological conditions, and discusses the therapeutic potential of macrophage-targeted strategies, aiming to provide theoretical guidance for precise modulation of macrophage function and the development of novel anti-fibrotic interventions.

Key words: macrophage, myocardial fibrosis, targeted therapy

CLC Number:

R363.2

Qian Yile, Yao Sai, Chen Sifeng, Li Quanfu, Zhao Meng. Research progress on the molecular mechanisms and targeted interventions of macrophage-mediated myocardial fibrosis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(3): 348-357.

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References 91

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