# Unraveling the Link: Ferroptosis and Its Implications in Cerebrovascular Diseases **Authors:** Zeran Yu, Jiabin Su, Xinjie Gao, Yuchao Fei, Meng Zhang, Junhui Qi, Wei Ni, Yuxiang Gu PMC · DOI: 10.3390/biom16020228 · Biomolecules · 2026-02-02 ## TL;DR This review explores how ferroptosis, a type of cell death, contributes to cerebrovascular diseases and highlights its potential as a therapeutic target. ## Contribution The paper provides a comprehensive overview of ferroptosis mechanisms and their implications in cerebrovascular diseases. ## Key findings - Ferroptosis is linked to the development of atherosclerosis, ischemic stroke, and hemorrhagic stroke. - Modulating ferroptosis pathways offers potential for new therapeutic strategies in cerebrovascular diseases. - The interplay between ferroptosis, oxidative stress, and inflammation is critical in disease progression. ## Abstract Cerebrovascular diseases, encompassing a spectrum of conditions affecting the blood vessels supplying the brain, represent a significant global health burden. Among the diverse mechanisms implicated in cerebrovascular pathology, emerging evidence highlights the role of ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation. The review also elucidates the molecular mechanisms underlying ferroptosis, emphasizing the pivotal role of iron, the intracellular antioxidant system, and lipid metabolism. Subsequently, it explores the growing body of literature implicating ferroptosis in the pathogenesis of various cerebrovascular diseases, including atherosclerosis, ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Special attention is given to the interplay between ferroptosis and other established mechanisms, such as oxidative stress, and inflammation. Moreover, pharmacological interventions and therapeutic strategies aimed at modulating key players in the ferroptosis cascade are explored, with a focus on their translational potential for clinical application. Finally, the review addresses current gaps in knowledge and proposes future research directions, emphasizing the need for a deeper understanding of the specific roles of ferroptosis in the pathogenesis of cerebrovascular diseases. The elucidation of these aspects holds promise for advancing our comprehension of cerebrovascular pathology and opening new avenues for therapeutic intervention in these debilitating conditions. ## Linked entities - **Diseases:** atherosclerosis (MONDO:0005311), ischemic stroke (MONDO:1060198), intracerebral hemorrhage (MONDO:0013792), subarachnoid hemorrhage (MONDO:0005099) ## Full-text entities - **Genes:** Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, SLC40A1 (solute carrier family 40 member 1) [NCBI Gene 30061] {aka FPN, FPN1, HFE4, IREG1, MST079, MSTP079}, P2RX7 (purinergic receptor P2X 7) [NCBI Gene 5027] {aka P2X7}, Slc7a11 (solute carrier family 7 (cationic amino acid transporter, y+ system), member 11) [NCBI Gene 26570] {aka 9930009M05Rik, sut, xCT}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, S100A4 (S100 calcium binding protein A4) [NCBI Gene 6275] {aka 18A2, 42A, CAPL, FSP1, MTS1, P9KA}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, SPHK1 (sphingosine kinase 1) [NCBI Gene 8877] {aka SPHK}, STEAP3 (STEAP3 metalloreductase) [NCBI Gene 55240] {aka AHMIO2, STMP3, TSAP6, dudlin-2, dudulin-2, pHyde}, DNTT (DNA nucleotidylexotransferase) [NCBI Gene 1791] {aka TDT}, Keap1 (kelch-like ECH-associated protein 1) [NCBI Gene 50868] {aka INRF2, mKIAA0132}, Hmox1 (heme oxygenase 1) [NCBI Gene 15368] {aka D8Wsu38e, HO-1, HO1, Hemox, Hmox, Hsp32}, 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}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, MT2A (metallothionein 2A) [NCBI Gene 4502] {aka MT-2, MT-II, MT2}, TERF1 (telomeric repeat binding factor 1) [NCBI Gene 7013] {aka PIN2, TRBF1, TRF, TRF1, hTRF1-AS, t-TRF1}, NOX4 (NADPH oxidase 4) [NCBI Gene 50507] {aka KOX, KOX-1, RENOX}, Dnmt3b (DNA methyltransferase 3B) [NCBI Gene 13436] {aka MmuIIIB}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, SLC11A2 (solute carrier family 11 member 2) [NCBI Gene 4891] {aka AHMIO1, DCT1, DMT1, NRAMP2}, USP14 (ubiquitin specific peptidase 14) [NCBI Gene 9097] {aka TGT, Ubp6}, GLS (glutaminase) [NCBI Gene 2744] {aka AAD20, CASGID, DEE71, EIEE71, GAC, GAM}, HAMP (hepcidin antimicrobial peptide) [NCBI Gene 57817] {aka HEPC, HFE2B, LEAP1, PLTR}, LPCAT3 (lysophosphatidylcholine acyltransferase 3) [NCBI Gene 10162] {aka C3F, LPCAT, LPLAT 5, LPLAT12, LPSAT, MBOAT5}, Elavl1 (ELAV like RNA binding protein 1) [NCBI Gene 15568] {aka 2410055N02Rik, HUR, Hua}, LOX (lysyl oxidase) [NCBI Gene 4015] {aka AAT10}, Aplnr (apelin receptor) [NCBI Gene 23796] {aka APJ, Agtrl1, msr/apj}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, UPF1 (UPF1 RNA helicase and ATPase) [NCBI Gene 5976] {aka HUPF1, NORF1, RENT1, UTF, pNORF1, smg-2}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, ALOX15 (arachidonate 15-lipoxygenase) [NCBI Gene 246] {aka 12-LOX, 15-LOX, 15-LOX-1, LOG15}, Pink1 (PTEN induced putative kinase 1) [NCBI Gene 68943] {aka 1190006F07Rik, BRPK, mFLJ00387}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, MPO (myeloperoxidase) [NCBI Gene 4353], DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, Snap25 (synaptosomal-associated protein 25) [NCBI Gene 20614] {aka Bdr, GENA70, SNAP-25, SUP, sp}, Trf (transferrin) [NCBI Gene 22041] {aka Cd176, HP, Tf, Tfn, hpx}, Gpx4 (glutathione peroxidase 4) [NCBI Gene 625249] {aka GPx-4, GSHPx-4, PHGPx, mtPHGPx, snGPx}, Satb1 (special AT-rich sequence binding protein 1) [NCBI Gene 20230] {aka 2610306G12Rik}, ACSL4 (acyl-CoA synthetase long chain family member 4) [NCBI Gene 2182] {aka ACS4, FACL4, LACS4, MRX63, MRX68, XLID63}, ALOX12 (arachidonate 12-lipoxygenase, 12S type) [NCBI Gene 239] {aka 12-LOX, 12S-LOX, LOG12}, TFAP2C (transcription factor AP-2 gamma) [NCBI Gene 7022] {aka AP2-GAMMA, ERF1, TFAP2G, hAP-2g}, NUP62 (nucleoporin 62) [NCBI Gene 23636] {aka IBSN, SNDI, p62}, ATF4 (activating transcription factor 4) [NCBI Gene 468] {aka CREB-2, CREB2, TAXREB67, TXREB}, HOTAIR (HOX transcript antisense RNA) [NCBI Gene 100124700] {aka HOXAS, HOXC-AS4, HOXC11-AS1, NCRNA00072}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, TFRC (transferrin receptor) [NCBI Gene 7037] {aka CD71, IMD46, T9, TFR, TFR1, TR}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, Slc3a2 (solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2) [NCBI Gene 17254] {aka 4F2, 4F2HC, Cd98, Ly-10, Ly-m10, Ly10}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, SLC1A1 (solute carrier family 1 member 1) [NCBI Gene 6505] {aka DCBXA, EAAC1, EAAT3, SCZD18, hEAAC1}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, SP1 (Sp1 transcription factor) [NCBI Gene 6667] - **Diseases:** acute (MESH:D000208), AIS (MESH:D000083242), ischemia (MESH:D007511), neurological dysfunction (MESH:D009461), metabolic (MESH:D008659), CSVD (MESH:D059345), iron dysregulation (MESH:D000090463), Cerebral vasospasm (MESH:D020301), vomiting (MESH:D014839), nausea (MESH:D009325), hemorrhage (MESH:D006470), brain edema (MESH:D001929), Intracranial atherosclerotic stenosis (MESH:D002537), stroke (MESH:D020521), aneurysmal rupture (MESH:D017542), rupture (MESH:D012421), diabetes (MESH:D003920), brain ischemia (MESH:D002545), brain infarction (MESH:D020520), calcification (MESH:D002114), malignancy (MESH:D009369), loss of consciousness (MESH:D014474), neural damage (MESH:D015441), aneurysm (MESH:D000783), neurotoxicity (MESH:D020258), neuroinflammation (MESH:D000090862), traumatic brain injury (MESH:D000070642), hyperlipidemia (MESH:D006949), cerebral microvasospasm (MESH:D002547), hematoma (MESH:D006406), hyperglycemia (MESH:D006943), neurodegenerative disorders (MESH:D019636), injury to (MESH:D014947), IA (MESH:D002532), headache (MESH:D006261), inflammation (MESH:D007249), Mitochondrial dysfunction (MESH:D028361), necrotic (MESH:D009336), impairments in executive function and memory (MESH:D008569), tissue injury (MESH:D017695), infarct (MESH:D007238), neuronal damage (MESH:D009410), vascular wall (MESH:D056988), Neurovascular Disease (MESH:D013901), ischemic injury (MESH:D017202), Ischemic Stroke (MESH:D002544), arterial stenosis (MESH:D012078), cardiovascular and cerebrovascular disease (MESH:D002318), neuronal and vascular injury (MESH:D057772), Cerebrovascular Diseases (MESH:D002561), thrombotic occlusion (MESH:D013927), SAH (MESH:D013345), nerve injury (MESH:D000080902), ICH (MESH:D002543), MCAO (MESH:D020244), Atherosclerosis (MESH:D050197), acute injury (MESH:D001930), neurological damage (MESH:D020196) - **Chemicals:** bleomycin (MESH:D001761), 4-HNE (MESH:C027576), glutamate (MESH:D018698), iron oxides (MESH:C000499), liproxstatin-1 (MESH:C000595890), Rhein (MESH:C020491), hydroxyl radicals (MESH:D017665), Artesunate (MESH:D000077332), vildagliptin (MESH:D000077597), cholesterol (MESH:D002784), pifithrin (MESH:C121565), water (MESH:D014867), phospholipid (MESH:D010743), arachidonic acid (MESH:D016718), Iron (MESH:D007501), carbon monoxide (MESH:D002248), Lipid Peroxide (MESH:D008054), coenzyme Q10 (MESH:C024989), deferoxamine (MESH:D003676), biliverdin (MESH:D001664), N-acetylneuraminic acid (MESH:D019158), hypochlorous acid (MESH:D006997), linoleic acid (MESH:D019787), paeonol (MESH:C013638), Fer-1 (MESH:C573944), Rosmarinic acid (MESH:C041376), 15, 16-Dihydrotanshinone I (MESH:C000713095), Icariside II (MESH:C060988), Baicalin (MESH:C038044), phenothiazine (MESH:C031637), ROS (MESH:D017382), ubiquinol (MESH:C003741), anthraquinone (MESH:D000880), GSH (MESH:D005978), glutamine (MESH:D005973), ATP (MESH:D000255), OH- (MESH:C031356), docosahexaenoic acid (MESH:D004281), Lipid (MESH:D008055), cysteine (MESH:D003545), amino acid (MESH:D000596), heme (MESH:D006418), fatty acyl-CoA (MESH:D000214), dUTP (MESH:C027078), Crocin (MESH:C029036), Dexmedetomidine (MESH:D020927), Selenium (MESH:D012643), fatty acid (MESH:D005227), sulfur (MESH:D013455), Melatonin (MESH:D008550), BODIPY 581/591 (-), hydrogen peroxide (MESH:D006861), cystine (MESH:D003553), erastin (MESH:C477224), beta-caryophyllene (MESH:C024714), PUFAs (MESH:D005231) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Scutellaria baicalensis (Baikal skullcap, species) [taxon 65409], Myristica fragrans (mace, species) [taxon 51089], Salvia miltiorrhiza (Chinese salvia, species) [taxon 226208], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606] - **Mutations:** JAK2V617F - **Cell lines:** HT-22 — Mus musculus (Mouse), Transformed cell line (CVCL_0321) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12938695/full.md ## Figures 2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938695/full.md ## References 148 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938695/full.md --- Source: https://tomesphere.com/paper/PMC12938695