收稿日期: 2025-08-06
录用日期: 2025-11-27
网络出版日期: 2026-03-30
基金资助
国家科技重大专项(2024ZD0526504);国家自然科学基金(82170238)
Research progress on the molecular mechanisms and targeted interventions of macrophage-mediated myocardial fibrosis
Received date: 2025-08-06
Accepted date: 2025-11-27
Online published: 2026-03-30
Supported by
National Science and Technology Major Project of the Ministry of Science and Technology of China(2024ZD0526504);National Natural Science Foundation of China(82170238)
心肌纤维化是多种心血管疾病发展的关键病理基础，其特征是成纤维细胞活化为肌成纤维细胞并大量合成胶原蛋白，导致细胞外基质异常积聚，进而损害心脏结构与功能。巨噬细胞作为心血管系统中的关键免疫细胞，其功能受到细胞来源和微环境变化的双重调控。不同表型的巨噬细胞在心肌损伤过程中发挥不同作用。促炎型巨噬细胞在早期介导炎症反应，而促修复型巨噬细胞则通过旁分泌因子促进成纤维细胞活化和胶原沉积。近年来，单细胞转录组与空间转录组等高通量技术的发展，以更高分辨率揭示了心脏巨噬细胞的异质性、动态变化及其与其他细胞的通信网络。传统治疗方法对心肌纤维化的疗效有限，而纳米颗粒递送系统或工程化细胞疗法等精准手段，可实现对心脏巨噬细胞的特异性重编程。该文总结心脏巨噬细胞的异质性，重点讨论在病理状态下巨噬细胞调控心肌纤维化的分子机制及其治疗潜力，旨在为精准调控巨噬细胞功能、开发心肌纤维化新疗法提供理论参考。
钱亦乐 , 姚赛 , 陈思锋 , 李全富 , 赵猛 . 巨噬细胞介导心肌纤维化的分子机制及靶向干预研究进展[J]. 上海交通大学学报（医学版）, 2026 , 46(3) : 348 -357 . DOI: 10.3969/j.issn.1674-8115.2026.03.009
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
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