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Growing evidence suggests that angiotensin receptor blockers (ARBs) have cardioprotective effects in DOX\u2010induced cardiomyopathy. However, the detailed mechanisms underlying the action of ARBs on the prevention of DOX\u2010induced cardiomyocyte cell death have yet to be investigated. Our results showed that angiotensin II receptor type I (AT<jats:sub>1<\/jats:sub>R) plays a critical role in DOX\u2010induced cardiomyocyte apoptosis. We found that MAPK signaling pathways, especially ERK1\/2, participated in modulating AT<jats:sub>1<\/jats:sub>R gene expression through DOX\u2010induced mitochondrial ROS release. These results showed that several potential heat shock binding elements (HSE), which can be recognized by heat shock factors (HSFs), located at the AT<jats:sub>1<\/jats:sub>R promoter region. HSF2 markedly translocated from the cytoplasm to the nucleus when cardiomyocytes were damaged by DOX. Furthermore, the DNA binding activity of HSF2 was enhanced by DOX via deSUMOylation. Overexpression of HSF2 enhanced DOX\u2010induced cardiomyocyte cell death as well. Taken together, we found that DOX induced mitochondrial ROS release to activate ERK\u2010mediated HSF2 nuclear translocation and AT<jats:sub>1<\/jats:sub>R upregulation causing DOX\u2010damaged heart failure in vitro and in vivo.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25905","type":"journal-article","created":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T21:18:13Z","timestamp":1489526293000},"page":"463-475","source":"Crossref","is-referenced-by-count":51,"title":["Mitochondrial ROS\u2010induced ERK1\/2 activation and HSF2\u2010mediated AT<sub>1<\/sub>R upregulation are required for doxorubicin\u2010induced cardiotoxicity"],"prefix":"10.1002","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0266-3233","authenticated-orcid":false,"given":"Chih\u2010Yang","family":"Huang","sequence":"first","affiliation":[{"name":"Translation Research Core China Medical University Hospital Taichung 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