# Exosome-delivered bioactive molecules regulate macrophage polarization in atherosclerosis and myocardial infarction: mechanisms and therapeutic potential **Authors:** Yuanlin Zhou, Guanghe Ran, Hua Guo PMC · DOI: 10.3389/fcvm.2026.1739907 · Frontiers in Cardiovascular Medicine · 2026-02-19 ## TL;DR This review explores how exosomes influence macrophage behavior in heart diseases, offering potential new treatments. ## Contribution The paper systematically summarizes how exosomes regulate macrophage polarization and their therapeutic potential in cardiovascular diseases. ## Key findings - Exosomes regulate M1/M2 macrophage polarization through specific bioactive molecules. - Exosomes can both promote and inhibit the progression of atherosclerosis and myocardial infarction. - Engineered exosomes and drug carriers show promise as new treatment strategies for cardiovascular diseases. ## Abstract Exosomes, by carrying biologically active molecules, constitute the core network of inter-cell communication and play an important role in the regulation of macrophage polarization. The dynamic balance of macrophage polarization is a key determinant of atherosclerosis plaque stability and cardiac repair after myocardial infarction. This review systematically summarizes the molecular mechanisms by which exosomes and their specific molecules accurately regulate M1/M2 polarization of macrophages. We also focused on the mechanism of action by which exosomes play a dual role in promoting or inhibiting the physiological and pathological environment of AS and MI. In addition, the clinical transformation potential and current challenges of new biomarkers and treatment strategies (such as engineered exosomes, drug carriers) are also discussed, which is expected to bring new treatment strategies to the treatment of cardiovascular diseases. ## Linked entities - **Diseases:** atherosclerosis (MONDO:0005311), myocardial infarction (MONDO:0005068) ## Full-text entities - **Genes:** ITGA3 (integrin subunit alpha 3) [NCBI Gene 3675] {aka CD49C, FRP-2, GAP-B3, GAPB3, ILNEB, JEB7}, TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189] {aka MGC:3310, RNF85}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], CXCR5 (C-X-C motif chemokine receptor 5) [NCBI Gene 643] {aka BLR1, CD185, MDR15}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, RAF1 (Raf-1 proto-oncogene, serine/threonine kinase) [NCBI Gene 5894] {aka CMD1NN, CRAF, NS5, Raf-1, c-Raf}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, SMAD7 (SMAD family member 7) [NCBI Gene 4092] {aka CRCS3, MADH7, MADH8}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CD47 (CD47 molecule) [NCBI Gene 961] {aka IAP, MER6, OA3}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, CD5L (CD5 molecule like) [NCBI Gene 922] {aka AIM, API6, CT-2, PRO229, SP-ALPHA, Spalpha}, PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 5563] {aka AMPK, AMPK2, AMPKa2, PRKAA}, MIR215 (microRNA 215) [NCBI Gene 406997] {aka MIRN215, miRNA215, mir-215}, MIR148A (microRNA 148a) [NCBI Gene 406940] {aka MIRN148, MIRN148A, hsa-mir-148, mir-148a}, JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, MIR1246 (microRNA 1246) [NCBI Gene 100302142] {aka MIRN1246, hsa-mir-1246}, PLCB3 (phospholipase C beta 3) [NCBI Gene 5331] {aka SMDCD}, SIRPA (signal regulatory protein alpha) [NCBI Gene 140885] {aka BIT, CD172A, MFR, MYD-1, MYD1, P84}, GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}, Jak2 (Janus kinase 2) [NCBI Gene 16452] {aka Fd17}, SOCS3 (suppressor of cytokine signaling 3) [NCBI Gene 9021] {aka ATOD4, CIS3, Cish3, SOCS-3, SSI-3, SSI3}, SPRY2 (sprouty RTK signaling antagonist 2) [NCBI Gene 10253] {aka IGAN3, hSPRY2}, CDK4 (cyclin dependent kinase 4) [NCBI Gene 1019] {aka CMM3, MCPH31, PSK-J3}, Nr5a1 (nuclear receptor subfamily 5, group A, member 1) [NCBI Gene 26423] {aka Ad4BP, ELP, ELP-3, Ftz-F1, Ftzf1, SF-1}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, LPAR1 (lysophosphatidic acid receptor 1) [NCBI Gene 1902] {aka EDG2, Gpcr26, LPA1, Mrec1.3, VZG1, edg-2}, MIR221 (microRNA 221) [NCBI Gene 407006] {aka MIRN221, miRNA221, mir-221}, AURKB (aurora kinase B) [NCBI Gene 9212] {aka AIK2, AIM-1, AIM1, ARK-2, ARK2, AurB}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, NOS3 (nitric oxide synthase 3) [NCBI Gene 4846] {aka EC-NOS, ECNOS, MYMY8, NOSIII, cNOS, eNOS}, SLC16A1 (solute carrier family 16 member 1) [NCBI Gene 6566] {aka HHF7, MCT, MCT1, MCT1D}, NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, MIR146A (microRNA 146a) [NCBI Gene 406938] {aka MIRN146, MIRN146A, miR-146a, miRNA146A}, MIR125A (microRNA 125a) [NCBI Gene 406910] {aka MIRN125A, miRNA125A, mir-125a}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, FASN (fatty acid synthase) [NCBI Gene 2194] {aka FAS, OA-519, SDR27X1}, MIR205 (microRNA 205) [NCBI Gene 406988] {aka MIRN205, mir-205}, MIR7704 (microRNA 7704) [NCBI Gene 102465802] {aka hsa-mir-7704}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, DUSP3 (dual specificity phosphatase 3) [NCBI Gene 1845] {aka VHR}, CD86 (CD86 molecule) [NCBI Gene 942] {aka B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, MIR26A1 (microRNA 26a-1) [NCBI Gene 407015] {aka MIR26A, MIRN26A1, mir-26a-1}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, RASD2 (RASD family member 2) [NCBI Gene 23551] {aka Rhes, TEM2}, Mir182 (microRNA 182) [NCBI Gene 387177] {aka Mirn182, mir-182, mmu-mir-182}, HYAL1 (hyaluronidase 1) [NCBI Gene 3373] {aka HYAL-1, LUCA1, MPS9, NAT6}, STAT2 (signal transducer and activator of transcription 2) [NCBI Gene 6773] {aka IMD44, ISGF-3, P113, PTORCH3, STAT113}, IL17RA (interleukin 17 receptor A) [NCBI Gene 23765] {aka CANDF5, CD217, CDw217, IL-17RA, IL17R, IMD51}, SOX6 (SRY-box transcription factor 6) [NCBI Gene 55553] {aka HSSOX6, SOXD, TOLCAS}, miR-4532 [NCBI Gene 100616353], CagA [NCBI Gene 48200769], SMPD3 (sphingomyelin phosphodiesterase 3) [NCBI Gene 55512] {aka NSMASE2}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, RAB6A (RAB6A, member RAS oncogene family) [NCBI Gene 5870] {aka RAB6} - **Diseases:** infarct (MESH:D007238), heart failure (MESH:D006333), cardiac (MESH:D006331), ovarian cancer (MESH:D010051), ventricular remodeling (MESH:D020257), necrotic (MESH:D009336), ESCC (MESH:D004938), HCC (MESH:D006528), sepsis (MESH:D018805), brucellosis (MESH:D002006), Glioblastoma (MESH:D005909), necrotic tissue (MESH:D017695), rheumatoid arthritis (MESH:D001172), liver metastasis (MESH:D009362), reperfusion injury (MESH:D015427), brain damage (MESH:D001925), CRC (MESH:D015179), AS (MESH:D050197), hyperglycemic (MESH:D006944), diabetic cardiomyopathy (MESH:D058065), death (MESH:D003643), colitis (MESH:D003092), ischemic stroke (MESH:D002544), AMI (MESH:D009203), infection (MESH:D007239), CVDs (MESH:D002318), toxicity (MESH:D064420), diseases of the heart and blood vessels (MESH:D009383), Gastric cancer (MESH:D013274), hypoxic (MESH:D002534), obesity (MESH:D009765), lung adenocarcinoma (MESH:D000077192), stroke (MESH:D020521), lung inflammation (MESH:D011014), tumorigenesis (MESH:D063646), COPD (MESH:D029424), myocardial damage (MESH:D009202), spinal cord injury (MESH:D013119), ischemia (MESH:D007511), metabolic abnormalities (MESH:D008659), hypoxia (MESH:D000860), oral squamous cell carcinoma (MESH:D000077195), glioma (MESH:D005910), myocardial fibrosis (MESH:D005355), periodontitis (MESH:D010518), gastric mucosal inflammation (MESH:D007249), mitochondrial dysfunction (MESH:D028361), Helicobacter pylori infection (MESH:D016481), cervical cancer (MESH:D002583), diabetes (MESH:D003920), ischemic (MESH:D002545), endothelial dysfunction (MESH:D014652), cancer (MESH:D009369), esophageal squamous cell carcinoma (MESH:D000077277), neuroinflammation (MESH:D000090862), lung injury (MESH:D055370), ACLR (MESH:D000070598), ALI (MESH:D055371) - **Chemicals:** ATP (MESH:D000255), LPS (MESH:D008070), lipid (MESH:D008055), nicorandil (MESH:D020108), ROS (MESH:D017382), folate (MESH:D005492), GW4869 (MESH:C468773), BMSC-EXO (-), ICA (MESH:C056599), nicotine (MESH:D009538), prostaglandin E2 (MESH:D015232), iron (MESH:D007501), ceramides (MESH:D002518), cholesterol (MESH:D002784), mannose (MESH:D008358), Ferrostatin-1 (MESH:C573944), alginate (MESH:D000464), paclitaxel (MESH:D017239), lactate (MESH:D019344), triglycerides (MESH:D014280) - **Species:** Helicobacter pylori (species) [taxon 210], Homo sapiens (human, species) [taxon 9606], Brucella (genus) [taxon 234], Mus musculus (house mouse, species) [taxon 10090] - **Cell lines:** VSMC — Homo sapiens (Human), Finite cell line (CVCL_4009), THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006), CT26 — Mus musculus (Mouse), Mouse colon adenocarcinoma, Cancer cell line (CVCL_7254) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12960621/full.md ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960621/full.md ## References 129 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960621/full.md --- Source: https://tomesphere.com/paper/PMC12960621