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Cardiomyocyte death in pathological cardiac conditions is the primary cause of heart failure and mortality. Our previous studies found that heat shock factor 1 (HSF1) protected cardiomyocytes from death by suppressing the IGF-IIR signaling pathway, which is critical for hypertensive angiotensin II-induced cardiomyocyte apoptosis. However, the role of heat shock factor 2 (HSF2) in hypertension-induced cardiac hypertrophy is unknown. We identified HSF2 as a miR-18 target for cardiac hypertrophy. p53 activation in angiotensin II (ANG II)-stimulated NRVMs is responsible for miR-18 downregulation both <jats:italic>i<\/jats:italic><jats:italic>n vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, which triggers HSF2 expression and the activation of IGF-IIR-induced cardiomyocyte hypertrophy. Finally, we provide genetic evidence that miR-18 is required for cardiomyocyte functions in the heart based on the gene transfer of cardiac-specific miR-18 <jats:italic>via<\/jats:italic> adenovirus-associated virus 2 (AAV2). Transgenic overexpression of miR-18 in cardiomyocytes is sufficient to protect against dilated cardiomyopathy during hypertension-induced heart failure. Our results demonstrated that the p53-miR-18-HSF2-IGF-IIR axis was a critical regulatory pathway of cardiomyocyte hypertrophy <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, suggesting that miR-18 could be a therapeutic target for the control of cardiac functions and the alleviation of cardiomyopathy during hypertension-induced heart failure.<\/jats:p>","DOI":"10.1038\/cddis.2017.320","type":"journal-article","created":{"date-parts":[[2017,8,10]],"date-time":"2017-08-10T12:41:59Z","timestamp":1502368919000},"page":"e2990-e2990","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["p53-mediated miR-18 repression activates HSF2 for IGF-IIR-dependent myocyte hypertrophy in hypertension-induced heart failure"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2347-0411","authenticated-orcid":false,"given":"Chih-Yang","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Ying","family":"Pai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Hua","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Jung","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Ying","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding-Yu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Jen","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V Vijaya","family":"Padma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Wen","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Yang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,10]]},"reference":[{"key":"BFcddis2017320_CR1","doi-asserted-by":"publisher","first-page":"7592","DOI":"10.1128\/MCB.14.11.7592","volume":"14","author":"PE Kroeger","year":"1994","unstructured":"Kroeger PE, Morimoto RI . 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