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We and others have reported the possibility of poly(ADP\u2010ribose) polymerase 1 (PARP1), the founding subtype of the PARPs enzyme family, as a novel therapeutic target of heart diseases. The cardiac fibrotic induction of mammalian target of rapamycin (mTOR) is mainly due to collagen expression, Smad3\u2010 and p53\/JNK\u2010mediated apoptosis. However, the possible link between PARP1 and mTOR in the progression of cardiac fibrosis remains unclear. In this study, PARP1 protein expression, and the activity of mTOR and its three target substrates (p70 ribosomal S6 Kinase 1, eukaryotic initiation factor 4E\u00ad\u2010binding protein 1, and UNC\u00ad51\u00adlike kinase 1) were augmented; meanwhile, the nicotinamide adenine dinucleotide (NAD) content was significantly reduced in the process of cardiac fibrosis in vivo and in vitro. Sprague\u2010Dawley rats were intraperitoneally injected with 3\u2010aminobenzamide (3AB) (20\u2009mg\/kg\/d; a well\u2010established PARP1 inhibitor) or rapamycin (Rapa; 1\u2009mg\/kg\/d; used for mTOR inhibition) 7 days after abdominal aortic constriction (AAC) surgery for 6 weeks. Pretreatment of 3AB or Rapa both relieved AAC\u2010caused cardiac fibrosis and heart dysfunction. Overexpression of PARP1 with adenovirus carrying PARP1 gene specifically transduced into the hearts via intramyocardial multipoint injection caused similar myocardial damage. In CFs, preincubation with PARP1 or mTOR inhibitors all blocked TGF\u2010\u03b21 induced cardiac fibrosis. PARP1 overexpression evoked cardiac fibrosis, which could be antagonized by mTOR inhibitors or NAD supplementation in CFs. These results provide novel and compelling evidence that PARP1 exacerbated cardiac fibrosis, which was partially attributed to NAD\u2010dependent activation of mTOR.<\/jats:p>","DOI":"10.1002\/jcb.26649","type":"journal-article","created":{"date-parts":[[2017,12,26]],"date-time":"2017-12-26T18:27:32Z","timestamp":1514312852000},"page":"4813-4826","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Poly(ADP\u2010ribose) polymerase 1 induces cardiac fibrosis by mediating mammalian target of rapamycin activity"],"prefix":"10.1002","volume":"120","author":[{"given":"Shuya","family":"Sun","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuehuai","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat\u2010sen University Guangzhou 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