# Poly(ADP-ribose) polymerase (PARP) inhibitors in cardiovascular, and cerebrovascular diseases: mechanisms, current trends and challenge for clinical translation **Authors:** Jinlin Fan, Yanfangfei Song PMC · DOI: 10.7717/peerj.20842 · PeerJ · 2026-02-20 ## TL;DR This review explores how PARP inhibitors, originally used for cancer, may also help treat cardiovascular and cerebrovascular diseases by examining their mechanisms and recent research. ## Contribution The paper highlights the expanding therapeutic potential of PARP inhibitors beyond oncology into cardiovascular and cerebrovascular diseases. ## Key findings - PARP inhibitors show promise in treating cardiovascular and cerebrovascular diseases. - Recent advancements in understanding PARP mechanisms could broaden their clinical applications. - Future research should focus on biomarkers and overcoming drug resistance for better clinical outcomes. ## Abstract Poly(ADP-ribose) polymerase (PARP) inhibitors constitute the inaugural targeted therapy shown to enhance the prognosis of individuals with hereditary tumors, initially utilized in the management of patients with germline BRCA1/2-associated breast cancer. With ongoing research, PARP inhibitors (PARPi) are currently under extensive investigation for their applicability across a spectrum of diseases, encompassing oncology, cardiovascular diseases, and cerebrovascular diseases. This narrative review provides a comprehensive synthesis of the biological rationale, existing evidence, recent advancements, and prospective future directions of PARPi in the treatment of cancers, cardiovascular diseases, and cerebrovascular disorders. We provide a comprehensive overview of the recent advancements, advantages, and limitations associated with both clinically approved and investigational PARPi. Beyond their application in oncology, PARPi demonstrate significant potential in other therapeutic domains, including cardiovascular diseases. As our comprehension of the biological functions of PARP and its molecular mechanisms advances, it is anticipated that the therapeutic applications of these inhibitors will broaden considerably. Future research endeavors should prioritize the identification of predictive biomarkers across various diseases and the development of strategies to circumvent drug resistance. Consequently, the integration of fundamental and clinical research on PARPi across diverse diseases is essential to establish a foundational framework for clinical translation. ## Linked entities - **Genes:** BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672], BRCA2 (BRCA2 DNA repair associated) [NCBI Gene 675] - **Proteins:** PARP1 (poly(ADP-ribose) polymerase 1) - **Diseases:** breast cancer (MONDO:0004989) ## Full-text entities - **Genes:** DUSP1 (dual specificity phosphatase 1) [NCBI Gene 1843] {aka CL100, HVH1, MKP-1, MKP1, PTPN10}, PARP12 (poly(ADP-ribose) polymerase family member 12) [NCBI Gene 64761] {aka ARTD12, MST109, MSTP109, ZC3H1, ZC3HDC1}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, ADORA2A (adenosine A2a receptor) [NCBI Gene 135] {aka A2aR, ADORA2, RDC8}, PRKCE (protein kinase C epsilon) [NCBI Gene 5581] {aka PKCE, nPKC-epsilon}, RAD51 (RAD51 recombinase) [NCBI Gene 5888] {aka BRCC5, FANCR, HRAD51, HsRad51, HsT16930, MRMV2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, NR1I2 (nuclear receptor subfamily 1 group I member 2) [NCBI Gene 8856] {aka BXR, ONR1, PAR, PAR1, PAR2, PARq}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, BNIP3L (BCL2 interacting protein 3 like) [NCBI Gene 665] {aka BNIP3a, NIP3L, NIX}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, MRE11 (MRE11 double strand break repair nuclease) [NCBI Gene 4361] {aka ATLD, HNGS1, MRE11A, MRE11B}, BARD1 (BRCA1 associated RING domain 1) [NCBI Gene 580], POLG (DNA polymerase gamma, catalytic subunit) [NCBI Gene 5428] {aka MIRAS, MTDPS4A, MTDPS4B, PEO, POLG1, POLGA}, RAP1A (RAP1A, member of RAS oncogene family) [NCBI Gene 5906] {aka C21KG, G-22K, KREV-1, KREV1, RAP1, SMGP21}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, LMNA (lamin A/C) [NCBI Gene 4000] {aka CDCD1, CDDC, CMD1A, CMT2B1, EMD2, FPL}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, SIRT6 (sirtuin 6) [NCBI Gene 51548] {aka SIR2L6, hSIRT6}, MUL1 (mitochondrial E3 ubiquitin protein ligase 1) [NCBI Gene 79594] {aka C1orf166, GIDE, MAPL, MULAN, RNF218}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, TRIP12 (thyroid hormone receptor interactor 12) [NCBI Gene 9320] {aka MRD49, TRIP-12, TRIPC, ULF}, MYLK (myosin light chain kinase) [NCBI Gene 4638] {aka AAT7, KRP, MLCK, MLCK1, MLCK108, MLCK210}, PRKCD (protein kinase C delta) [NCBI Gene 5580] {aka ALPS3, CVID9, MAY1, PKCD, nPKC-delta}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, AGT (angiotensinogen) [NCBI Gene 183] {aka ANHU, SERPINA8, hFLT1}, TP53BP1 (tumor protein p53 binding protein 1) [NCBI Gene 7158] {aka 53BP1, TDRD30, p202, p53BP1}, H1-0 (H1.0 linker histone) [NCBI Gene 3005] {aka H1.0, H10, H1F0, H1FV}, SELP (selectin P) [NCBI Gene 6403] {aka CD62, CD62P, GMP140, GRMP, LECAM3, PADGEM}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, PARP2 (poly(ADP-ribose) polymerase 2) [NCBI Gene 10038] {aka ADPRT2, ADPRTL2, ADPRTL3, ARTD2, PARP-2, pADPRT-2}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 3480] {aka CD221, IGFIR, IGFR, JTK13}, NBN (nibrin) [NCBI Gene 4683] {aka AT-V1, AT-V2, ATV, NBS, NBS1, P95}, XRCC1 (X-ray repair cross complementing 1) [NCBI Gene 7515] {aka RCC, SCAR26}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, SP1 (Sp1 transcription factor) [NCBI Gene 6667], MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, GJA1 (gap junction protein alpha 1) [NCBI Gene 2697] {aka AVSD3, CMDR, CX43, EKVP, EKVP3, GJAL}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, AIFM1 (apoptosis inducing factor mitochondria associated 1) [NCBI Gene 9131] {aka AIF, AUNX1, CMT2D, CMTX4, COWCK, COXPD6}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, PARP9 (poly(ADP-ribose) polymerase family member 9) [NCBI Gene 83666] {aka ARTD9, BAL, BAL1, MGC:7868}, Gja1 (gap junction protein, alpha 1) [NCBI Gene 24392] {aka Cx43, Cxnk1}, RAD50 (RAD50 double strand break repair protein) [NCBI Gene 10111] {aka NBSLD, RAD502, hRad50}, PALB2 (partner and localizer of BRCA2) [NCBI Gene 79728] {aka BROVCA5, FANCN, PNCA3}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, 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], FOXO3 (forkhead box O3) [NCBI Gene 2309] {aka AF6q21, FKHRL1, FKHRL1P2, FOXO2, FOXO3A}, PARP14 (poly(ADP-ribose) polymerase family member 14) [NCBI Gene 54625] {aka ARTD8, BAL2, PARP-14, pART8} - **Diseases:** HR-deficient cancers (MESH:D009369), diabetes (MESH:D003920), cerebral ischemia (MESH:D002545), pulmonary diseases (MESH:D008171), Endothelial dysfunction (MESH:D014652), Huntington's disease (MESH:D006816), neuroinflammation (MESH:D000090862), hemorrhagic stroke (MESH:D000083302), CF (MESH:D003550), traumatic brain injury (MESH:D000070642), cardiac arrest (MESH:D006323), cardiometabolic and neurovascular diseases (MESH:D024821), hyperglycemia (MESH:D006943), fibrosis (MESH:D005355), inflammation (MESH:D007249), neurodegenerative diseases (MESH:D019636), injury (MESH:D014947), circulatory shock (MESH:D012769), mitochondrial (MESH:D028361), pancreatic cancer (MESH:D010190), myocardial remodeling (MESH:D064752), MDS (MESH:D009190), hematologic malignancies (MESH:D019337), AML (MESH:D015470), cardiotoxicity (MESH:D066126), cardiac ischemia (MESH:D007511), motor deficits (MESH:D009461), hypoxia (MESH:D000860), non- (MESH:C580335), non-small cell lung cancer (MESH:D002289), hereditary tumors (MESH:D013132), brain swelling (MESH:D001929), tumorigenesis (MESH:D063646), stroke (MESH:D020521), uveitis (MESH:D014605), HR (MESH:C535296), Cardiomyopathy (MESH:D009202), neurobehavioral and neurochemical abnormalities (MESH:D019954), colitis (MESH:D003092), cerebral infarction (MESH:D002544), myocardial hypertrophy (MESH:D006984), Ischemic diseases (MESH:D017202), dilated cardiomyopathy (MESH:D002311), cardiovascular and cerebrovascular diseases (MESH:D002318), MI (MESH:D009203), hemorrhagic shock (MESH:D012771), cytotoxic (MESH:D064420), cardio- and cerebrovascular diseases (MESH:D002561), I/R injury (MESH:D015427), metastasis (MESH:D009362), restenosis (MESH:D023903), mitochondrial collapse (MESH:D001261), Vascular calcification (MESH:D061205), middle cerebral artery occlusion (MESH:D020244), Atherosclerosis (MESH:D050197), ICH (MESH:D002543), cardiomyocyte death (MESH:D003643), ovarian and breast cancer (MESH:D061325), carcinogenic (MESH:D011230), hypertension (MESH:D006973) - **Chemicals:** lactam (MESH:D007769), JPI-289 (MESH:C000625768), lipid peroxides (MESH:D008054), ADP (MESH:D000244), Veliparib (MESH:C521013), AZD5305 (MESH:C000722772), nitric oxide (MESH:D009569), Rucaparib (MESH:C531549), nicotinamide (MESH:D009536), amide (MESH:D000577), nucleotide (MESH:D009711), iron (MESH:D007501), 4-Aminobenzoic Acid (MESH:D010129), PD128763 (MESH:C068870), creatine phosphate (MESH:D010725), NU1025 (MESH:C115774), RBN-3143 (-), H2O2 (MESH:D006861), Pamiparib (MESH:C000707927), DOX (MESH:D004317), Fluzoparib (MESH:C000722917), MP-124 (MESH:C560412), 4-AN (MESH:C086538), hydrogen (MESH:D006859), RNS (MESH:D011886), NAD+ (MESH:D009243), ROS (MESH:D017382), glucose (MESH:D005947), Talazoparib (MESH:C586365), ATP (MESH:D000255), PJ-34 (MESH:C434926), Olaparib (MESH:C531550), Niraparib (MESH:C545685), quinazoline (MESH:D011799), 3-AB (MESH:C025160) - **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Cercopithecidae (monkey, family) [taxon 9527] - **Mutations:** A2A - **Cell lines:** umbilical — Homo sapiens (Human), Finite cell line (CVCL_B5ZH), WRL-68 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0581) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12927604/full.md ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12927604/full.md ## References 188 references — full list in the complete paper: https://tomesphere.com/paper/PMC12927604/full.md --- Source: https://tomesphere.com/paper/PMC12927604