REVIEW article
Front. Med.
Sec. Pathology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1664538
Macrophage Metabolism in Inflammatory Heart Disease: New Insights and Therapeutic Implications
Provisionally accepted
- 1Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2Liyuan Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
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Macrophages are essential immune cells involved in pathogen clearance, initiation and resolution of inflammation, and tissue repair across multiple organ systems. They exhibit remarkable phenotypic diversity, encompassing classical M1 and M2 subtypes-further subdivided into M2a, M2b, M2c, and M2d-as well as newly identified subsets such as Mreg, M4, Mox, and Mhem, each with distinct functional roles. Emerging evidence highlights cellular metabolism as a central regulator of macrophage phenotype and function. Distinct metabolic programs underpin the polarization of M1 and M2 macrophages in response to environmental cues, thereby critically influencing disease progression and tissue outcomes. Cardiovascular disease remains a leading cause of morbidity and mortality worldwide. In the heart, macrophages represent a dominant immune cell population and play integral roles in both pathological injury and tissue regeneration. This review provides a comprehensive overview of macrophage ontogeny, phenotypic heterogeneity, and metabolic reprogramming, with a particular focus on their roles in inflammatory heart diseases. We synthesize current findings on how metabolic pathways shape macrophage behavior and function within the cardiac microenvironment and discuss the therapeutic potential of targeting macrophage metabolism to modulate inflammation, promote repair, and improve clinical outcomes in cardiovascular disease.
Keywords: Inflammatory, Heart, Disease, macrophage, metabolic, reprogramming, Immunometabolism, Therapeutic targeting
Received: 12 Jul 2025; Accepted: 18 Sep 2025.
Copyright: © 2025 Zhang, Xiang, Chang, Zhou, Jin and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xi Zhang, zhangxi798@sina.com
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