# Research progress on macrophage regulation of atherosclerosis **Authors:** Jiahui Song, Rui Yan, Ping Li, Jincheng Guo, Guangyao Zhai, Jing Li PMC · DOI: 10.3389/fcvm.2026.1682994 · Frontiers in Cardiovascular Medicine · 2026-02-04 ## TL;DR This paper reviews how macrophages contribute to atherosclerosis and explores current research on their role in plaque development and potential treatments. ## Contribution The paper provides a comprehensive review of macrophage mechanisms in atherosclerosis and recent therapeutic strategies. ## Key findings - Macrophages play a key role in initiating and promoting atherosclerosis plaque development. - Research is focused on understanding macrophage-driven plaque instability and identifying therapeutic targets. - Recent advances aim to treat and prevent atherosclerosis through macrophage regulation. ## Abstract Cardiovascular diseases (CVDs) currently are responsible for high disability and mortality rates worldwide. Atherosclerosis is a major pathological process leading to CVDs, and macrophages are known to be important contributors to the initiation of atherosclerosis and promotion of plaque development, which eventually leads to plaque rupture. The role of these cells as a driver of plaque instability has received widespread attention, with continued research efforts devoted to unraveling the underlying mechanisms of macrophage involvement in atherosclerosis and identifying specific therapeutic strategies. In this review, we summarize the current evidence regarding the mechanisms by which macrophages regulate the progression of plaque development as well as recent therapeutic advances for the treatment and prevention of atherosclerosis. ## Linked entities - **Diseases:** atherosclerosis (MONDO:0005311) ## Full-text entities - **Genes:** MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, NR0B2 (nuclear receptor subfamily 0 group B member 2) [NCBI Gene 8431] {aka SHP, SHP1}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Xaf1 (XIAP associated factor 1) [NCBI Gene 327959] {aka Fbox39}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Traf6 (TNF receptor-associated factor 6) [NCBI Gene 22034] {aka 2310003F17Rik, C630032O20Rik}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, S100A9 (S100 calcium binding protein A9) [NCBI Gene 6280] {aka 60B8AG, CAGB, CFAG, CGLB, L1AG, LIAG}, MIAT (myocardial infarction associated transcript) [NCBI Gene 440823] {aka C22orf35, GOMAFU, LINC00066, NCRNA00066, RNCR2, lncRNA-MIAT}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, MIR204 (microRNA 204) [NCBI Gene 406987] {aka MIRN204, RDICC, miRNA204, mir-204}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Cd40lg (CD40 ligand) [NCBI Gene 21947] {aka CD154, CD40-L, Cd40l, HIGM1, IGM, IMD3}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Mir21a (microRNA 21a) [NCBI Gene 387140] {aka Mir21, Mirn21, mmu-mir-21, mmu-mir-21a}, Il1a (interleukin 1 alpha) [NCBI Gene 16175] {aka Il-1a}, Lyve1 (lymphatic vessel endothelial hyaluronan receptor 1) [NCBI Gene 114332] {aka 1200012G08Rik, Crsbp-1, Lyve-1, Xlkd1}, S100A8 (S100 calcium binding protein A8) [NCBI Gene 6279] {aka 60B8AG, CAGA, CFAG, CGLA, CP-10, L1Ag}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, Ccl4 (C-C motif chemokine ligand 4) [NCBI Gene 20303] {aka AT744.1, Act-2, MIP-1B, Mip1b, Scya4}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, RICTOR (RPTOR independent companion of MTOR complex 2) [NCBI Gene 253260] {aka AVO3, PIA, hAVO3}, Bcl6 (B cell leukemia/lymphoma 6) [NCBI Gene 12053] {aka Bcl5}, EPHB2 (EPH receptor B2) [NCBI Gene 2048] {aka BDPLT22, CAPB, DRT, EK5, EPHT3, ERK}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Mir215 (microRNA 215) [NCBI Gene 387211] {aka Mirn215, mir-215, mmu-mir-215}, EGR1 (early growth response 1) [NCBI Gene 1958] {aka AT225, G0S30, KROX-24, NGFI-A, TIS8, ZIF-268}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, ABCA1 (ATP binding cassette subfamily A member 1) [NCBI Gene 19] {aka ABC-1, ABC1, CERP, HDLCQTL13, HDLDT1, HPALP1}, KLF4 (KLF transcription factor 4) [NCBI Gene 9314] {aka EZF, GKLF}, Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, Mir155 (microRNA 155) [NCBI Gene 387173] {aka Mirn155, mir-155, mmu-mir-155}, CD47 (CD47 molecule) [NCBI Gene 961] {aka IAP, MER6, OA3}, Irf5 (interferon regulatory factor 5) [NCBI Gene 27056] {aka mirf5}, DNASE2 (deoxyribonuclease 2, lysosomal) [NCBI Gene 1777] {aka AIPCS, DNASE2A, DNL, DNL2}, Apoe (apolipoprotein E) [NCBI Gene 11816] {aka Apo-E}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, Mir181a-1 (microRNA 181a-1) [NCBI Gene 735252] {aka Mirn181a-1, Mirn213, miR-213, mir-181a-1, mmu-mir-213}, Cd40 (CD40 antigen) [NCBI Gene 21939] {aka Bp50, GP39, HIGM1, IGM, IMD3, T-BAM}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, Clec4a2 (C-type lectin domain family 4, member a2) [NCBI Gene 26888] {aka Clec4a, Clecsf6, DCIR, Dcir1}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, SIRPA (signal regulatory protein alpha) [NCBI Gene 140885] {aka BIT, CD172A, MFR, MYD-1, MYD1, P84}, Trem2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 83433] {aka TREM-2, Trem2a, Trem2b, Trem2c}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, S100A12 (S100 calcium binding protein A12) [NCBI Gene 6283] {aka CAAF1, CAGC, CGRP, ENRAGE, MRP-6, MRP6}, Map3k5 (mitogen-activated protein kinase kinase kinase 5) [NCBI Gene 26408] {aka 7420452D20Rik, ASK, ASK1, MAPKKK5, Mekk5}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, CSF1 (colony stimulating factor 1) [NCBI Gene 1435] {aka CSF-1, MCSF, PG-M-CSF}, Or6a2 (olfactory receptor family 6 subfamily A member 2) [NCBI Gene 18317] {aka I7, MOR103-15, Olfr2, Olfr41}, PRKDC (protein kinase, DNA-activated, catalytic subunit) [NCBI Gene 5591] {aka DNA-PKC, DNA-PKcs, DNAPK, DNAPKc, DNPK1, HYRC} - **Diseases:** sudden cardiac death (MESH:D016757), ACS (MESH:D054058), Coronary Lesion (MESH:D003327), inflammation (MESH:D007249), fibrosis (MESH:D005355), diabetes (MESH:D003920), plaque rupture (MESH:D012421), plaque (MESH:D003773), dysfunction (MESH:D006331), tissue injury (MESH:D017695), TCFA (MESH:D058226), intimal injury (MESH:C563733), necrotic (MESH:D009336), Atherosclerosis (MESH:D050197), Thrombosis (MESH:D013927), EIMP (MESH:D055501), toxicity (MESH:D064420), myocardial infarction (MESH:D009203), CVDs (MESH:D002318) - **Chemicals:** cholesterol (MESH:D002784), octanal (MESH:C031639), CLA (MESH:D044243), chitosan (MESH:D048271), Linoleic acid (MESH:D019787), mannose (MESH:D008358), -deoxycholic acid (MESH:D003840), polyethylene glycol (MESH:D011092), LPS (MESH:D008070), lipid (MESH:D008055), glycol (MESH:D006018), reactive oxygen species (MESH:D017382), rosiglitazone (MESH:D000077154), lobeglitazone (MESH:C546215), Canakinumab (MESH:C541220), Ca2+ (-), catecholamine (MESH:D002395), carbon nanotubes (MESH:D037742) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606] ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12913517/full.md ## Figures 2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12913517/full.md ## References 73 references — full list in the complete paper: https://tomesphere.com/paper/PMC12913517/full.md --- Source: https://tomesphere.com/paper/PMC12913517