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Hypertension-induced pressure overload triggers left ventricular hypertrophy and leads to heart failure. Although the precise mechanisms remain incompletely elucidated, recent studies highlighted the role of ubiquitin-proteasome system in this process. As a heart tissue-enriched E3 ligase, the function of Asb10 in cardiac hypertrophy remains unknown. Here, we aimed to dissect the role of Asb10 in the pathogenesis of cardiac hypertrophy and heart failure. Through integrated bioinformatic screening of GEO datasets and experimental verifications, we identified Asb10 as the downregulated gene in cardiac hypertrophy. Adenoviral overexpression of Asb10 exacerbated hypertrophic growth in NRVMs treated with phenylephrine or endothelin-1. Mechanistically, immunoprecipitation\u2013mass spectrometry and co-immunoprecipitation assays revealed that Asb10 binds HSP70 and competitively blocks STUB1-mediated ubiquitination and degradation of HSP70, thereby stabilizing HSP70. Pharmacological or small interfering RNA-induced inhibition of HSP70 partially reversed Asb10 overexpression-induced hypertrophic growth in NRVMs. In vivo, mice administrated with AAV9-\n                    <jats:italic>Asb10<\/jats:italic>\n                    exhibited worse cardiac function and more severe interstitial fibrosis following TAC surgery, while mice injected with AAV9-\n                    <jats:italic>shAsb10<\/jats:italic>\n                    showed improved outcomes. Furthermore, we observed that the effects of Asb10 on cardiac hypertrophy were attributed to the elevation of HSP70, cardiac inflammation, and activation of pHDAC2\n                    <jats:sup>S394<\/jats:sup>\n                    . Collectively, these findings demonstrate that Asb10 stabilizes HSP70 via competitively inhibiting STUB1-mediated ubiquitin-dependent degradation, thereby exacerbating cardiac hypertrophy, highlighting the role of Asb10 in hemodynamic stress-induced cardiac hypertrophy and heart failure.\n                  <\/jats:p>","DOI":"10.1038\/s41419-025-07735-5","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T21:31:59Z","timestamp":1747863119000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Asb10 accelerates pathological cardiac remodeling by stabilizing HSP70"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8156-0576","authenticated-orcid":false,"given":"Ke","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songzan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4484-219X","authenticated-orcid":false,"given":"Yingchao","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingchen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4606-2835","authenticated-orcid":false,"given":"Yanbo","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongying","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0199-3353","authenticated-orcid":false,"given":"Chenyang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7027-0717","authenticated-orcid":false,"given":"Guosheng","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0582-2102","authenticated-orcid":false,"given":"Qinfeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"7735_CR1","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/s41569-018-0007-y","volume":"15","author":"M Nakamura","year":"2018","unstructured":"Nakamura M, Sadoshima J. 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