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PARP7 negatively regulates the IFN\u2010I signaling pathway through a mono\u2010ADP\u2010ribosylation\u2010dependent interaction with TBK1. Here, through comprehensive analysis of the expression profile of the PARP family in LPS\u2010treated myocardial tissues, we propose that PARP7 may be associated with septic cardiomyopathy. Then, we demonstrate that PARP7 deficiency exacerbates LPS\u2010induced septic cardiomyopathy in vivo. Integrated single\u2010nucleus and single\u2010cell RNA sequencing analyses demonstrate that PARP7 is predominantly upregulated in macrophages in the hearts of LPS\u2010treated mice. Using an AAV9\u2010based delivery system, we further validated the cardioprotective role of macrophage\u2010specific PARP7 in murine models of sepsis induced by either LPS or CLP. Mechanistically, PARP7 interacts with TBK1 to mediate its ADP\u2010ribosylation, thereby suppressing the TBK1\u2010driven inflammatory response in macrophages. The snRNA\u2010seq and cytokine array data collectively support a critical role for PARP7 as a molecular \u201cbrake\u201d that constrains excessive macrophage inflammation. In conclusion, this work identifies a macrophage\u2010specific PARP7\u2010TBK1 regulatory axis in septic cardiomyopathy and highlights the therapeutic potential of macrophage\u2010specific PARP7 overexpression.<\/jats:p>","DOI":"10.1002\/advs.77404","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:14:09Z","timestamp":1787584449000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage PARP7 Alleviates Septic Cardiomyopathy by Interacting With TBK1 and Suppressing TBK1\u2010Driven Inflammatory Response"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-3469","authenticated-orcid":false,"given":"Jibo","family":"Han","sequence":"first","affiliation":[{"name":"The Key Laboratory the Second Affiliated Hospital of Jiaxing University  Jiaxing Zhejiang China"},{"name":"Department of Cardiology the Second Affiliated Hospital of Jiaxing University  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