{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T15:59:54Z","timestamp":1777564794822,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T00:00:00Z","timestamp":1428451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81370260, 81371450, 81170321"],"award-info":[{"award-number":["81370260, 81371450, 81170321"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pathological cardiac hypertrophy often leads to heart failure. Activation of autophagy has been shown in pathological hypertrophic hearts. Autophagy is regulated positively by Class III phosphoinositide 3\u2010kinase (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K). However, it is unknown whether Class III <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K plays a role in the transition of cardiac hypertrophy to heart failure. To address this question, we employed a previously established cardiac hypertrophy model in heat shock protein 27 transgenic mice which shares common features with several types of human cardiomyopathy. Age\u2010matched wild\u2010type mice served as control. Firstly, a prolonged activation of autophagy, as reflected by autophagosome accumulation, increased <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3 conversion and decreased p62 protein levels, was detected in hypertrophic hearts from adaptive stage to maladaptive stage. Moreover, morphological abnormalities in myofilaments and mitochondria were presented in the areas accumulated with autophagosomes. Secondly, activation of Class III <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K Vacuolar protein sorting 34 (Vps34), as demonstrated by upregulation of Vps34 expression, increased interaction of Vps34 with Beclin\u20101, and deceased Bcl\u20102 expression, was demonstrated in hypertrophic hearts from adaptive stage to maladaptive stage. Finally, administration with Wortmaninn, a widely used autophagy inhibitor by suppressing Class III <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K activity, significantly decreased autophagy activity, improved morphologies of intracellular apartments, and most importantly, prevented progressive cardiac dysfunction in hypertrophic hearts. Collectively, we demonstrated that Class III <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K plays a central role in the transition of cardiac hypertrophy to heart failure <jats:italic>via<\/jats:italic> a prolonged activation of autophagy in current study. Class III <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K may serve as a potential target for the treatment and management of maladaptive cardiac hypertrophy.<\/jats:p>","DOI":"10.1111\/jcmm.12547","type":"journal-article","created":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T07:07:26Z","timestamp":1428476846000},"page":"1710-1719","source":"Crossref","is-referenced-by-count":34,"title":["Class III <scp>PI<\/scp>3K\u2010mediated prolonged activation of autophagy plays a critical role in the transition of cardiac hypertrophy to heart failure"],"prefix":"10.1111","volume":"19","author":[{"given":"Peng","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Geriatrics First Affiliated Hospital with Nanjing Medical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics First Affiliated Hospital with Nanjing Medical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanfu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery East Tennessee State University Johnson City TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuehua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Nanjing Medical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics First Affiliated Hospital with Nanjing Medical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics First Affiliated Hospital with Nanjing Medical University Nanjing 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