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In the heart, reactive oxygen species are linked with cardiac ischemia\/reperfusion injury, hypertrophy, and heart failure. While this correlation between ROS and cardiac pathology has been observed in multiple models of heart failure, the independent role of hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) in vitro and in vivo is unclear, owing to a lack of tools for precise manipulation of intracellular redox state. Here we apply a chemogenetic system based on a yeast D-amino acid oxidase to show that chronic generation of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> in the heart induces a dilated cardiomyopathy with significant systolic dysfunction. We anticipate that chemogenetic approaches will enable future studies of in vivo H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> signaling not only in the heart, but also in the many other organ systems where the relationship between redox events and physiology remains unclear.<\/jats:p>","DOI":"10.1038\/s41467-018-06533-2","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T13:34:08Z","timestamp":1537968848000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":129,"title":["Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1329-6547","authenticated-orcid":false,"given":"Benjamin","family":"Steinhorn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3172-0284","authenticated-orcid":false,"given":"Andrea","family":"Sorrentino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0771-3711","authenticated-orcid":false,"given":"Sachin","family":"Badole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Bogdanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vsevolod","family":"Belousov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Michel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,2]]},"reference":[{"key":"6533_CR1","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nri3423","volume":"13","author":"C Nathan","year":"2013","unstructured":"Nathan, C. & Cunningham-Bussel, A. 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