Macrophage trafficking and efferocytosis in atherosclerotic plaque regression: Molecular mechanisms and therapeutic perspectives - 20/09/26
, Maedeh Bordbar c, 2 , Saghi Eslamzadeh d, e, 3 , Fatemeh Hosseinpour-Soleimani d, f, 4 , Amir Tajbakhsh g, ⁎, 5 , Amir Savardashtaki c, h, ⁎, 6 , Armin Attar i, ⁎, 7 Abstract |
Atherosclerosis is characterized by the accumulation of plaques within arterial walls, with plaque progression and regression being dynamically influenced by macrophage behavior. This review examines the roles of macrophage trafficking and efferocytosis in atherosclerotic plaque regression, with particular emphasis on macrophage retention, egress, and the clearance of apoptotic cells. Retention of macrophages within plaques, mediated by regulators such as Netrin-1 and Semaphorin-3E, contributes to persistent inflammation and impaired plaque resolution. In contrast, macrophage egress through pathways involving CCR7 and CCL19 can promote inflammatory resolution and facilitate the removal of apoptotic cells. Effective efferocytosis is essential for maintaining tissue homeostasis, whereas its dysregulation contributes to continued inflammation and atherosclerosis progression. The review further discusses therapeutic strategies aimed at modulating macrophage behavior, including macrophage polarization, mTOR signaling, LXR activation, cholesterol efflux, and targeted approaches to enhance macrophage function. By integrating these mechanisms, this review highlights the interconnected roles of macrophage trafficking and efferocytosis in plaque regression and discusses their therapeutic potential for the development of strategies to promote atherosclerotic plaque resolution.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Macrophage dynamics in atherosclerotic plaque progression and regression. Schematic illustrating the balance between monocyte recruitment, macrophage retention, efferocytosis, and egress during plaque progression and regression. In plaque progression, endothelial activation promotes monocyte recruitment, while inflammatory macrophages accumulate lipid, persist within the lesion, and defective efferocytosis drives necrotic core expansion, fibrous cap thinning, and plaque instability. In plaque regression, reduced monocyte recruitment, pro-resolving macrophage reprogramming, efficient efferocytosis, enhanced cholesterol efflux (ABCA1/ABCG1), and CCR7- and S1P1-mediated macrophage egress reduce inflammation, limit necrotic core size, strengthen the fibrous cap, and promote plaque stabilization and regression. Abbreviations: ABCA1, ATP-binding cassette transporter A1; ABCG1, ATP-binding cassette transporter G1; CCL2, C-C motif chemokine ligand 2; CCR2, C-C chemokine receptor 2; CCR7, C-C chemokine receptor 7; ICAM-1, intercellular adhesion molecule-1; IL-10, interleukin-10; S1P1, sphingosine-1-phosphate receptor 1; TGF-β, transforming growth factor-beta; VCAM-1, vascular cell adhesion molecule-1.
Macrophage dynamics in atherosclerotic plaque progression and regression. Schematic illustrating the balance between monocyte recruitment, macrophage retention, efferocytosis, and egress during plaque progression and regression. In plaque progression, endothelial activation promotes monocyte recruitment, while inflammatory macrophages accumulate lipid, persist within the lesion, and defective efferocytosis drives necrotic core expansion, fibrous cap thinning, and plaque instability. In plaque regression, reduced monocyte recruitment, pro-resolving macrophage reprogramming, efficient efferocytosis, enhanced cholesterol efflux (ABCA1/ABCG1), and CCR7- and S1P1-mediated macrophage egress reduce inflammation, limit necrotic core size, strengthen the fibrous cap, and promote plaque stabilization and regression. Abbreviations: ABCA1, ATP-binding cassette transporter A1; ABCG1, ATP-binding cassette transporter G1; CCL2, C-C motif chemokine ligand 2; CCR2, C-C chemokine receptor 2; CCR7, C-C chemokine receptor 7; ICAM-1, intercellular adhesion molecule-1; IL-10, interleukin-10; S1P1, sphingosine-1-phosphate receptor 1; TGF-β, transforming growth factor-beta; VCAM-1, vascular cell adhesion molecule-1. Le texte complet de cet article est disponible en PDF.
Highlights |
• | Macrophage trafficking and efferocytosis regulate atherosclerotic plaque progression and regression. |
• | Macrophage retention contributes to inflammation, necrosis, and plaque instability. |
• | Impaired efferocytosis promotes necrotic core expansion and persistent inflammation. |
• | mTOR, LXR, HDL, and ALDH2 influence macrophage phenotype and lipid handling. |
• | Targeting macrophage migration, metabolism, and miRNAs may promote plaque regression. |
Abbreviations : ABCA1, ABCG1, ACs, Arg1, ACE, Akt, ALDH2, AMPK, AngII, ApoA-I, ApoE, BM-MC, BMS, CCL, CCL2, CCR, CCR2, CD36, CD68, CGAS, CVD, CX3CR1, CXCL4, CypA, DALY, DES, ECM, GATA2, GLUT1, GXK, GRP78, HFD, HDL, HIF, HP-β-CD, HMG-CoA, HSYA, ICAM-1, IFNAR1, IFN-γ, IHD, IL, IL-1β, IL-6, IL-10, iNOS, ITreg, JAK, Ldlr , LDL, LOX-1, LPC, LPS, LRP1, LXR, M(Hb)/Mhem, MerTK, MI, MIAT, MMP, MTOR, MiR, MSR1, NE, NTreg, OxLDL, PAD, PAR, PCI, PHLIP, PFKFB2, PHD, PLGA, PM 2.5 , PPARγ, PEG, PS PtdSer, Rac1, RAS, RCAN1, RCT, RvD1, ROS, S/V, S1P, siRNA, SIRPα, SIRT1, SMC, SPMs, SR-A, SR-BI, STAT, STING, TGF-β, TLR4, TNF-α, Treg, TREM2, TC, TXNIP, USP14, VCAM-1, VEGF, VEGFR, VNS, VSMCs, WD, α7nAChR, rHDL, KLF4, GM3, MCP-1
Keywords : Atherosclerosis, Macrophage trafficking, Macrophage egress, Plaque regression, Efferocytosis, Macrophage retention, Cholesterol efflux, Macrophage-targeted therapy
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Vol 203
Article 119872- octobre 2026 Retour au numéro
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