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The pathogenesis of DOX-induced cardiomyopathy (DiCM) is yet to be elucidated. Increasing studies proved that activation of AKT prevented cardiomyocyte apoptosis and cardiac dysfunction in response to DOX insult. Our previous studies indicated that major vault protein (MVP) deficiency was accompanied by suppressed phosphorylation of AKT in metabolic diseases. This study aimed to investigate the role and underlying mechanism of MVP on cardiomyocyte apoptosis in DiCM.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Mice were intraperitoneally injected with DOX 5\u00a0mg\/kg, once a week for 5\u00a0weeks, the total cumulative dose was 25\u00a0mg\/kg. Cardiomyocyte-specific MVP overexpression was achieved using an adeno-associated virus system under the cTnT promoter after the fourth DOX injection. Cardiac function was examined by echocardiography followed by euthanasia. Tissue and serum were collected for morphology analysis and biochemical examination.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Herein, we found that MVP expression was upregulated in DOX-treated murine hearts. Cardiac-specific MVP overexpression alleviated DOX-induced cardiac dysfunction, oxidative stress and fibrosis. Mechanistically, MVP overexpression activated AKT signaling and decreased  cardiomyocyte\u00a0apoptosis\u00a0in DiCM.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Based on these findings, we supposed that MVP was a potential therapeutic agent against DiCM.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12872-022-02517-9","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T13:38:34Z","timestamp":1646401114000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Major vault protein attenuates cardiomyocyte injury in doxorubicin-induced cardiomyopathy through activating AKT"],"prefix":"10.1186","volume":"22","author":[{"given":"Yu","family":"Qi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhou","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"issue":"24","key":"2517_CR1","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1016\/j.jacc.2009.02.050","volume":"53","author":"ET Yeh","year":"2009","unstructured":"Yeh ET, Bickford CL. 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This study did not involve human participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics and consent to participate"}},{"value":"The study was carried out in compliance with the ARRIVE guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"ARRIVE statement"}},{"value":"Not required. This manuscript does not include any data relating to an individual person.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"77"}}