# DAB2IP: unifying cardiovascular pathogenesis and cardiovascular brain crosstalk **Authors:** Yufan Zhou, Peiwen Yang, Hanxun He, Hao Liu, Ping Ye, Jiahong Xia PMC · DOI: 10.3389/fcvm.2026.1660204 · 2026-02-03 ## TL;DR The DAB2IP gene plays a key role in linking cardiovascular diseases and brain disorders through multiple biological pathways. ## Contribution This paper highlights DAB2IP as a unifying factor in cardiovascular and neurological pathogenesis and crosstalk. ## Key findings - DAB2IP regulates inflammation, apoptosis, and plaque angiogenesis in atherosclerosis via multiple signaling pathways. - DAB2IP is genetically linked to coronary artery disease, aortic aneurysm, and aortic dissection. - DAB2IP influences brain processes like neuron migration and blood-brain barrier integrity in Alzheimer's disease models. ## Abstract Cardiovascular diseases and brain disorders collectively represent a major global health burden. Not only do they frequently occur as comorbidities, but their pathological mechanisms are also intricately linked through a complex network of cardiovascular-brain crosstalk. Cardiovascular diseases (CVDs) and neurological disorders together impose high global health burdens. The DAB2IP gene, initially characterized as a tumor suppressor, serves as a multifunctional regulator and performs roles in both the cardiovascular and neurological systems. In atherosclerosis (AS), DAB2IP suppresses the inflammation and apoptosis of endothelial cells (ECs) through the TNF signaling pathways, inhibits phenotypic switching of vascular smooth muscle cells (VSMCs) via the JAK-STAT and PI3K-Akt axes, and attenuates plaque angiogenesis via VEGF-related pathways. It is genetically associated with coronary artery disease (CAD), aortic aneurysm (AA), and aortic dissection (AD) risk, and mediates hemodynamic stress responses and glucose/lipid metabolic dysregulation in the vasculature. In the cardiovascular brain circuit (CBC), DAB2IP governs cortical neuron migration through the Rap1-integrin pathways, modulates the integrity of the blood-brain barrier (BBB) in Alzheimer's disease models via apoptosis-related signaling, and associates with arterial adventitial immune-neural remodeling. Newly developed DAB2IP-targeted strategies, including epigenetic modulators and engineered exosomal circRNA delivery systems, demonstrate preclinical potential but require rigorous validation in various models to assess long-term biosafety and organ-specific efficacy. ## Linked entities - **Genes:** DAB2IP (DAB2 interacting protein) [NCBI Gene 153090] - **Diseases:** atherosclerosis (MONDO:0005311), coronary artery disease (MONDO:0005010), aortic aneurysm (MONDO:0005160), Alzheimer's disease (MONDO:0004975) ## Full-text entities - **Genes:** Icam1 (intercellular adhesion molecule 1) [NCBI Gene 15894] {aka CD54, Icam-1, Ly-47, MALA-2}, TRAF2 (TNF receptor associated factor 2) [NCBI Gene 7186] {aka MGC:45012, RNF117, TRAP, TRAP3}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, RELN (reelin) [NCBI Gene 5649] {aka ETL7, LIS2, PRO1598, RL}, HSPG2 (heparan sulfate proteoglycan 2) [NCBI Gene 3339] {aka HSPG, PLC, PRCAN, SJA, SJS, SJS1}, HTRA2 (HtrA serine peptidase 2) [NCBI Gene 27429] {aka MGCA8, OMI, PARK13, PRSS25}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, MIR323A (microRNA 323a) [NCBI Gene 442897] {aka MIR323, MIRN323, hsa-mir-323, hsa-mir-323a, mir-323a}, Cd68 (CD68 antigen) [NCBI Gene 12514] {aka Lamp4, Scard1, gp110}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Dab2ip (DAB2 interacting protein) [NCBI Gene 192126] {aka AIP-1, DIP1/2}, PLK1 (polo like kinase 1) [NCBI Gene 5347] {aka PLK, STPK13}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, MAP1B (microtubule associated protein 1B) [NCBI Gene 4131] {aka DFNA83, FUTSCH, MAP5, PPP1R102, PVNH9}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 116554] {aka JNK}, DBP (D-box binding PAR bZIP transcription factor) [NCBI Gene 1628] {aka DABP, taxREB302}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714] {aka ASV, SRC1, THC6, c-SRC, p60-Src}, Traf2 (TNF receptor-associated factor 2) [NCBI Gene 22030], ETS1 (ETS proto-oncogene 1, transcription factor) [NCBI Gene 2113] {aka ETS-1, EWSR2, c-ets-1, p54}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, XBP1 (X-box binding protein 1) [NCBI Gene 7494] {aka TREB-5, TREB5, XBP-1, XBP2}, ARF6 (ARF GTPase 6) [NCBI Gene 382], ESR2 (estrogen receptor 2) [NCBI Gene 2100] {aka ER-BETA, ESR-BETA, ESRB, ESTRB, Erb, NR3A2}, KIF3A (kinesin family member 3A) [NCBI Gene 11127] {aka FLA10, KLP-20}, Ern1 (endoplasmic reticulum to nucleus signalling 1) [NCBI Gene 78943] {aka 9030414B18Rik, Ire1a, Ire1alpha, Ire1p}, Cxcl10 (C-X-C motif chemokine ligand 10) [NCBI Gene 15945] {aka C7, CRG-2, INP10, IP-10, IP10, Ifi10}, NFIC (nuclear factor I C) [NCBI Gene 4782] {aka CTF, CTF5, NF-I, NF-I/C, NF1-C, NFI}, 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}, CYBB (cytochrome b-245 beta chain) [NCBI Gene 1536] {aka AMCBX2, CGD, CGDX, GP91-1, GP91-PHOX, GP91PHOX}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, AKR1C3 (aldo-keto reductase family 1 member C3) [NCBI Gene 8644] {aka DD3, DDX, HA1753, HAKRB, HAKRe, HSD17B5}, TRADD (TNFRSF1A associated via death domain) [NCBI Gene 8717] {aka Hs.89862}, NTN1 (netrin 1) [NCBI Gene 9423] {aka MRMV4, NET1, NTN1L}, PIK3R2 (phosphoinositide-3-kinase regulatory subunit 2) [NCBI Gene 5296] {aka MPPH, MPPH1, P85B, p85, p85-BETA, p85beta}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, Xbp1 (X-box binding protein 1) [NCBI Gene 22433] {aka D11Ertd39e, TREB-5, TREB5, XBP-1}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, RHOA (ras homolog family member A) [NCBI Gene 387] {aka ARH12, ARHA, EDFAOB, RHO12, RHOH12}, HIPK1 (homeodomain interacting protein kinase 1) [NCBI Gene 204851] {aka Myak, Nbak2}, RAP1A (RAP1A, member of RAS oncogene family) [NCBI Gene 5906] {aka C21KG, G-22K, KREV-1, KREV1, RAP1, SMGP21}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, DAB2 (DAB adaptor protein 2) [NCBI Gene 1601] {aka DOC-2, DOC2}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, TERF2IP (TERF2 interacting protein) [NCBI Gene 54386] {aka DRIP5, RAP1}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, NLRP12 (NLR family pyrin domain containing 12) [NCBI Gene 91662] {aka CLR19.3, FCAS2, NALP12, PAN6, PYPAF7, RNO} - **Diseases:** BBB (MESH:C536830), AA (MESH:D001014), neuroinflammation (MESH:D000090862), Alzheimer's (MESH:D000544), impairment of (MESH:D060825), arteriosclerosis (MESH:D001161), aneurysms (MESH:D000783), endothelial dysfunction (MESH:D014652), diabetic (MESH:D003920), AD (MESH:D000784), rupture (MESH:D012421), large vessel disease (MESH:C536223), cancers (MESH:D009369), pain (MESH:D010146), coronary lesions (MESH:D003327), premature ovarian failure (MESH:D016649), intracranial aneurysm (MESH:D002532), neurodegenerative diseases (MESH:D019636), Disease (MESH:D004194), HL (MESH:C538324), inflammation (MESH:D007249), fibrosis (MESH:D005355), hyperlipidemia (MESH:D006949), aortic diseases (MESH:D001018), prostate cancer (MESH:D011471), cardiogenic stroke (MESH:D013575), cardiocerebrovascular disorders (MESH:D009358), neurofibrillary tangles (MESH:D055956), Hypoxia (MESH:D000860), neurological disorders (MESH:D009461), MDD (MESH:D003865), small vessel disease (MESH:D059345), metabolic disorders (MESH:D008659), AAAs (MESH:C536008), cardiomyopathies (MESH:D009202), Stroke (MESH:D020521), Stanford type A (MESH:D006969), noncommunicable disease (MESH:D000073296), cerebral amyloid angiopathy (MESH:D016657), postoperative organ dysfunction (MESH:D009102), hypoxic (MESH:D002534), obese (MESH:D009765), SVC (MESH:D013479), endothelial injury (MESH:D057772), cerebrovascular disease (MESH:D002561), insulin resistance (MESH:D007333), myocardial infarction (MESH:D009203), CVDs (MESH:D002318), aneurysm dilation (MESH:D002311), ischemic stroke (MESH:D002544), CS (MESH:D006223), vascular dementia (MESH:D015140), brain disorders (MESH:D001927), hypertension (MESH:D006973), deaths (MESH:D003643), post-menopausal myocardial infarction (MESH:D015663), AS (MESH:D050197), AAA (MESH:D017544), cardio-cerebral comorbidities (MESH:D044542), restenosis (MESH:D023903) - **Chemicals:** adrenaline (MESH:D004837), PIP2 (MESH:D019269), oxygen (MESH:D010100), fat (MESH:D005223), nitric oxide (MESH:D009569), testosterone (MESH:D013739), IP3 (MESH:D015544), phosphatidylinositol 4-phosphate (MESH:C037178), amyloid-beta1-42 (-), glucose (MESH:D005947), ROS (MESH:D017382), calcium (MESH:D002118), dehydroepiandrosterone (MESH:D003687), lipid (MESH:D008055), carbon dioxide (MESH:D002245) - **Species:** Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Mus musculus (house mouse, species) [taxon 10090], Nicotiana tabacum (American tobacco, species) [taxon 4097], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Bos taurus (bovine, species) [taxon 9913] - **Mutations:** rs7025486, G>a, rs885150, rs35061590, rs13290547, rs10818576, rs587936, G to A, rs3798220 ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960645/full.md --- Source: https://tomesphere.com/paper/PMC12960645