[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-358730-105":3,"detail-sidebar-cat-0-en-105":79,"doc-detail-358730-en":129},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":72,"head_meta":74,"extra_data":76,"updated_unix":78},105,"en","polyadp-ribose-polymerase-parp-inhibitors-in-cardiovascular-and-cerebrovascular-diseases-mechanisms-current-trends-and-challenge-for-clinical-translation","Poly(ADP-ribose) polymerase (PARP) inhibitors in cardiovascular, and cerebrovascular diseases - mechanisms, current trends and challenge for clinical translation","","Poly(ADP-ribose) polymerase (PARP) inhibitors represent an established targeted approach that improves outcomes in hereditary tumors, first used for germline BRCA1/2-associated breast cancer. Ongoing studies extend PARP inhibitors (PARPi) to cardiovascular and cerebrovascular diseases. This narrative review synthesizes biological rationale, evidence, recent advances, and future clinical-translation directions, covering both approved and investigational PARPi. It highlights ongoing needs for predictive biomarkers and strategies to overcome drug resistance for broad integration of basic and clinical research.",{"@graph":14,"@context":71},[15,34,54],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/polyadp-ribose-polymerase-parp-inhibitors-in-cardiovascular-and-cerebrovascular-diseases-mechanisms-current-trends-and-challenge-for-clinical-translation/358730/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":48,"encodingFormat":47,"isAccessibleForFree":49,"interactionStatistic":50},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/polyadp-ribose-polymerase-parp-inhibitors-in-cardiovascular-and-cerebrovascular-diseases-mechanisms-current-trends-and-challenge-for-clinical-translation/358730.png","ImageObject",300,407,{"name":42,"@type":43},"Ezra","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-23",true,{"@type":51,"interactionType":52,"userInteractionCount":30},"InteractionCounter",{"@type":53},"ViewAction",{"@type":55,"mainEntity":56},"FAQPage",[57,63,67],{"name":58,"@type":59,"acceptedAnswer":60},"What role do PARP inhibitors play in disease treatment according to the review?","Question",{"text":61,"@type":62},"PARP inhibitors block PARylation and impair DNA damage response, supporting targeted therapy. The review also discusses their potential beyond oncology, including cardiovascular diseases and cerebrovascular disorders.","Answer",{"name":64,"@type":59,"acceptedAnswer":65},"How does PARP1 contribute to DNA damage repair under different levels of genomic stress?",{"text":66,"@type":62},"Under moderate damage, PARP1 acts as an early sensor and promotes base excision repair. Under severe damage, excessive PARP1 activation depletes NAD+ and ATP, disrupts repair protein recruitment, increases ROS, and shifts toward a pro-death signal.",{"name":68,"@type":59,"acceptedAnswer":69},"What are the main priorities for future research in PARPi clinical translation?",{"text":70,"@type":62},"The review emphasizes identifying predictive biomarkers across diseases and developing strategies to circumvent drug resistance. It also stresses integrating basic and clinical findings to establish a foundation for translation.","https://schema.org",{"og:url":32,"og:type":73,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":75,"canonical":32},"index,follow",{"doc_id":77,"site_id":7},358730,1790153982,{"code":4,"msg":80,"data":81},"success",[82,86,90,94,99,104,109,113,118,121,125],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":83,"show_sort_weight":84,"slug":85},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":87,"show_sort_weight":88,"slug":89},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":91,"show_sort_weight":92,"slug":93},"Exam",70,"exam",{"id":95,"doc_module":4,"doc_module_name":25,"category_name":96,"show_sort_weight":97,"slug":98},5,"Comic",60,"comic",{"id":100,"doc_module":4,"doc_module_name":25,"category_name":101,"show_sort_weight":102,"slug":103},6,"Technology",50,"technology",{"id":105,"doc_module":4,"doc_module_name":25,"category_name":106,"show_sort_weight":107,"slug":108},7,"Healthcare",40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":111,"slug":112},8,30,"research-report",{"id":114,"doc_module":4,"doc_module_name":25,"category_name":115,"show_sort_weight":116,"slug":117},9,"Religion & Spirituality",20,"religion-spirituality",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":119,"show_sort_weight":116,"slug":120},"World Cup","world-cup",{"id":122,"doc_module":4,"doc_module_name":25,"category_name":123,"show_sort_weight":122,"slug":124},10,"Lifestyle","lifestyle",{"id":126,"doc_module":4,"doc_module_name":25,"category_name":127,"show_sort_weight":95,"slug":128},19,"General","general",{"code":4,"msg":80,"data":130},{"doc_id":77,"user_id":131,"nickname":42,"user_avatar":132,"doc_module":4,"category_id":110,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":30,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":138,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144},1099514068035,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Submitted 11 September 2025 Accepted 5 January 2026 Published 20 February 2026  \nCorresponding author Yanfangfei Song,  \n[a15804079363@126.com](a15804079363@126.com)[ ](a15804079363@126.com)Academic editor Faiza Farhan  \nAdditional Information and Declarations can be found on page 22  \nDOI 10.7717/peerj.20842  Copyright  \n2026 Fan and Song  \nDistributed under  \nCreative Commons CC-BY 4.0  \nPoly(ADP-ribose) polymerase (PARP) inhibitors in cardiovascular, and cerebrovascular diseases: mechanisms, current trends and challenge for clinical translation  \nJinlin Fan and Yanfangfei Song  \nShengjing Hospital of China Medical University, China Medical University, Shenyang, China  \nABSTRACT  \nPoly(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.  \nSubjects Biochemistry, Cardiology, Clinical Trials, Drugs and Devices, Oncology Keywords PARP1, Cardiovascular diseases, Cerebrovascular diseases, PARP inhibitor  \nINTRODUCTION  \nPoly(ADP-ribose) polymerases (PARPs) constitute a family of nuclear proteins comprising 17 members that perform critical cellular functions. Their core mechanism involves PARylation (poly-ADP-ribosylation), through which they auto-modify and modify DNA damage response (DDR) proteins. This post-translational modification enables PARPs to orchestrate essential biological processes including DNA repair, gene transcription regulation, and modulation of cell death pathways (Huang & Kraus, 2022) .  \nHow to cite this article Fan J, Song Y. 2026. Poly(ADP-ribose) polymerase (PARP) inhibitors in cardiovascular, and cerebrovascular diseases: mechanisms, current trends and challenge for clinical translation. PeerJ 14:e20842 DOI 10.7717/peerj.20842  \nUnder physiological conditions, PARPs are the critical mediator for maintaining cellular homeostasis. They primarily localize within the nucleus and maintains tight chromatin association, actively participating in diverse biological processes including DDR (recognizing and repairing both single-strand breaks (SSBs) and double-strand breaks (DSBs)), chromosomal stability maintenance, transcriptional regulation, and cellular proliferation and differentiation (Morales et al., 2014; Rodríguez et al., 2015; Verdone et al., 2015; Xu et al., 2014) . PARP1 is the predominant isoform of the PARPs family, with PARP1 accounting for 85–90% of total cellular PARylation activity (Xu et al., 2014) . PARP1 and PARP2 both participate in DNA repair, however, PARP2 lacks the N-terminal DNA-binding domain","cbCaigSN9hto9DXG","https://ap.wps.com/l/cbCaigSN9hto9DXG","pdf",5673405,37,"English","# Abstract\n# Introduction\n## PARPs family and PARylation mechanism\n## PARP1 dual role in DNA damage response\n## Clinical application focus on anticancer therapy","[{\"question\":\"What role do PARP inhibitors play in disease treatment according to the review?\",\"answer\":\"PARP inhibitors block PARylation and impair DNA damage response, supporting targeted therapy. The review also discusses their potential beyond oncology, including cardiovascular diseases and cerebrovascular disorders.\"},{\"question\":\"How does PARP1 contribute to DNA damage repair under different levels of genomic stress?\",\"answer\":\"Under moderate damage, PARP1 acts as an early sensor and promotes base excision repair. Under severe damage, excessive PARP1 activation depletes NAD+ and ATP, disrupts repair protein recruitment, increases ROS, and shifts toward a pro-death signal.\"},{\"question\":\"What are the main priorities for future research in PARPi clinical translation?\",\"answer\":\"The review emphasizes identifying predictive biomarkers across diseases and developing strategies to circumvent drug resistance. It also stresses integrating basic and clinical findings to establish a foundation for translation.\"}]","Poly(ADP-ribose) polymerase (PARP) inhibitors in cardiovascular, and cerebrovascular diseases - mechanisms, current trends and challenge for clinical translation | PDF",1790135097,93]