Academic Journal
SIRT3 in post-myocardial infarction macrophage reprogramming: linking mitochondrial fitness to inflammation resolution and repair.
| Τίτλος: | SIRT3 in post-myocardial infarction macrophage reprogramming: linking mitochondrial fitness to inflammation resolution and repair. |
|---|---|
| Συγγραφείς: | Li X; Qihuang College, Guizhou University of Traditional Chinese Medicine, Guiyang, China., Luo X; School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China., Zhang Z; School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China., Tang L; School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China., Meng X; Qihuang College, Guizhou University of Traditional Chinese Medicine, Guiyang, China. |
| Πηγή: | Frontiers in immunology [Front Immunol] 2026 Jul 08; Vol. 17, pp. 1848626. Date of Electronic Publication: 2026 Jul 08 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article; Review; Systematic Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| Ιατρικοί όροι (MeSH): | Macrophages*/metabolism , Macrophages*/immunology , Myocardial Infarction*/metabolism , Myocardial Infarction*/pathology , Myocardial Infarction*/immunology , Sirtuin 3*/metabolism , Mitochondria*/metabolism , Cellular Reprogramming*, Inflammation/metabolism ; Inflammation/immunology ; Reactive Oxygen Species/metabolism ; Humans ; Animals ; Efferocytosis ; Metabolic Reprogramming |
| Περίληψη: | Myocardial infarction (MI) remains a leading cause of cardiovascular mortality worldwide. Despite significant advances in reperfusion strategies and pharmacotherapy, persistent inflammation and adverse ventricular remodeling continue to underlie poor long-term clinical outcomes. Macrophages serve as central orchestrators of post-MI healing, coordinating the clearance of necrotic debris, resolution of inflammation, remodeling of the extracellular matrix, and maturation of the fibrotic scar. However, the conventional M1/M2 dichotomy fails to fully capture the dynamic, phenotypically heterogeneous, and metabolically constrained macrophage states that emerge during infarct healing. In this review, we synthesize current evidence supporting a trajectory-based framework for macrophage reprogramming following MI and emphasize mitochondrial fitness as a critical determinant governing the transition from sustained inflammation to reparative resolution. We summarize key metabolic checkpoints regulating this functional shift-including glycolytic rewiring, tricarboxylic acid (TCA) cycle remodeling, mitochondrial reactive oxygen species (mtROS) accumulation, efferocytosis, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and mitochondrial quality control. Furthermore, we advance the hypothesis that SIRT3-the principal mitochondrial NAD+-dependent deacetylase-may act as a central regulatory node linking mitochondrial protein acetylation to macrophage state transitions after MI. Specifically, we outline a staged dual-axis working model, generated from convergent but largely indirect evidence, in which the SOD2-mtROS axis is more closely linked to early nonresolving inflammation, whereas the PDHA1-metabolic flexibility axis may be more relevant to efferocytosis-associated reparative transition. We further highlight NAD+ availability as an upstream limiting factor that may constrain SIRT3 activity in macrophages under ischemic-inflammatory stress. Finally, we critically evaluate the current evidence hierarchy, human translatability, therapeutic strategies, and key translational challenges-emphasizing considerations of timing, cellular specificity, delivery modalities, and target engagement. Although macrophage-specific causal evidence in myocardial infarction (MI) remains sparse, this framework is intended as a mechanistically coherent and experimentally tractable working hypothesis to guide future investigations into macrophage immunometabolism and mitochondrial-targeted interventions in post-infarction cardiac repair. Accordingly, the proposed framework should be viewed as a testable working hypothesis rather than a settled causal model of macrophage fate control in MI. (Copyright © 2026 Li, Luo, Zhang, Tang and Meng.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
| Contributed Indexing: | Keywords: NAD+; SIRT3; efferocytosis; immunometabolism; inflammation resolution; macrophage reprogramming; mitochondrial fitness; myocardial infarction |
| Substance Nomenclature: | EC 3.5.1.- (Sirtuin 3) 0 (Reactive Oxygen Species) |
| Entry Date(s): | Date Created: 20260723 Date Completed: 20260723 Latest Revision: 20260723 |
| Update Code: | 20260723 |
| PubMed Central ID: | PMC13388082 |
| DOI: | 10.3389/fimmu.2026.1848626 |
| PMID: | 42488660 |
| Βάση Δεδομένων: | MEDLINE |
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