{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:21:24Z","timestamp":1787574084175,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cardiac hypertrophy is a common phenomenon observed in progressive heart disease associated with heart failure. Insulin\u2010like growth factor receptor II (IGF\u2010IIR) has been much implicated in myocardial hypertrophy. Our previous studies have found that increased activities of signaling mediators, such as calcium\/calmodulin\u2010dependent protein kinase II (CaMKII) and calcineurin induces pathological hypertrophy. Given the critical roles played by CaMKII and calcineurin signaling in the progression of maladaptive hypertrophy, we anticipated that inhibition of CaMKII and calcineurin signaling may attenuate IGF\u2010IIR\u2010induced cardiac hypertrophy. The current study, therefore, investigated the effects of IGF\u2010IIR activation on the CaMKII and calcineurin signaling and whether the combinatorial inhibition of the CaMKII\u03b4 and calcineurin signaling could ameliorate IGF\u2010IIR\u2010induced pathological hypertrophy. In the present study, we induced IGF\u2010IIR through the cardiomyocyte\u2010specific transduction of IGFII\n                    <jats:sup>Y27L<\/jats:sup>\n                    via adeno\u2010associated virus 2 (AAV2) to evaluate its effects on cardiac hypertrophy. Interestingly, it was observed that the activation of IGF\u2010IIR signaling through IGFII\n                    <jats:sup>Y27L<\/jats:sup>\n                    induces significant hypertrophy of the myocardium and increased cardiac apoptosis and fibrosis. Moreover, we found that Leu\n                    <jats:sup>27<\/jats:sup>\n                    IGF\u2010II significantly induced calcineurin and CaMKII expression. Furthermore and importantly, the combinatorial treatment with CaMKII and calcineurin inhibitors significantly alleviates IGF\u2010IIR\u2010induced hypertrophic responses. Thus, it could be envisaged that the inhibition of IGF\u2010IIR may serve as a promising candidate for attenuating maladaptive hypertrophy. Both calcineurin and CaMKII could be valuable targets for developing treatment strategies against hypertension\u2010induced cardiomyopathies.\n                  <\/jats:p>","DOI":"10.1002\/jcp.29242","type":"journal-article","created":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T06:28:55Z","timestamp":1570170535000},"page":"3539-3547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The combined inhibition of the CaMKII\u03b4 and calcineurin signaling cascade attenuates IGF\u2010IIR\u2010induced cardiac hypertrophy"],"prefix":"10.1002","volume":"235","author":[{"given":"Chung\u2010Hao","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute of Aging Medicine China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Science China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0266-3233","authenticated-orcid":false,"given":"Chih\u2010Yang","family":"Huang","sequence":"additional","affiliation":[{"name":"Translation Research Core China Medical University Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Lan","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Pathology Changhua Christian Hospital  Changhua Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia\u2010Yao","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Nursing Mei Ho University  Pingtung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9030-4152","authenticated-orcid":false,"given":"Khan Farheen","family":"Badrealam","sequence":"additional","affiliation":[{"name":"Cardiovascular and Mitochondria Related Diseases Research Center, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation  Hualien Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung\u2010Jung","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Tzu Chi University  Hualien Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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