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Calsyntenin-1(CLSTN1) plays a critical role in the nervous system, but its relevance in cardiovascular diseases is unknown. We investigated the significance of CLSTN1 in doxorubicin-induced DCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CLSTN1 expression in doxorubicin-induced DCM rats and H9c2 cells was determined using western blotting. To further explore the functions of CLSTN1, a cardiac-specific CLSTN1 overexpression rat model was constructed. The rats were subjected to analysis using echocardiographic, hemodynamic, and electrocardiographic parameters. Potential downstream molecules in CLSTN1 overexpression heart tissue were investigated using proteomics and western blotting. Finally, a knockdown of CLSTN1 was constructed to investigate the rescue function on doxorubicin-induced cell toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CLSTN1 protein expression increased drastically in doxorubicin-induced DCM rats and H9c2 cells. Under doxorubicin treatment, CLSTN1 protein-specific overexpression in the heart muscle promoted cardiac chamber enlargement and heart failure, while the knockdown of CLSTN1 reduced doxorubicin-induced cardiomyocyte toxicity in vitro. At the mechanistic level, overexpression of CLSTN1 downregulated SERCA2 expression and increased the phosphorylation levels of PI3K-Akt and CaMK2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrated that CLSTN1 promotes the pathogenesis of doxorubicin-induced DCM. CLSTN1 could be a therapeutic target to prevent the development of doxorubicin-induced DCM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10557-022-07389-x","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T08:02:58Z","timestamp":1667980978000},"page":"237-252","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Calsyntenin-1 Promotes Doxorubicin-induced Dilated Cardiomyopathy in Rats"],"prefix":"10.1007","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6435-8659","authenticated-orcid":false,"given":"Mingxiang","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liting","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanying","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunlun","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"7389_CR1","doi-asserted-by":"publisher","first-page":"112623","DOI":"10.1016\/j.msec.2021.112623","volume":"133","author":"NA D\u2019Angelo","year":"2022","unstructured":"D\u2019Angelo NA, Noronha MA, C\u00e2mara MCC, Kurnik IS, Feng C, Araujo VHS, et al. 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