{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:51:57Z","timestamp":1780098717384,"version":"3.54.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T00:00:00Z","timestamp":1633305600000},"content-version":"vor","delay-in-days":276,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470510"],"award-info":[{"award-number":["81470510"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2020JM-029"],"award-info":[{"award-number":["2020JM-029"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Recent studies reported that miR\u2010128 was differentially expressed in cardiomyocytes in response to pathologic stress. However, its function and mechanism remain to be fully elucidated. The aim of the present study was to investigate the role of miR\u2010128 in chronic angiotensin II (Ang II) infusion\u2010induced cardiac remodeling and its underlying mechanism. The cardiac remodeling and heart failure in vivo were established in C57BL\/6 mice by chronic subcutaneous Ang II delivery. Knocking down miR\u2010128 was conducted in the hearts of the mice by intravenous injection of HBAAV2\/9\u2010miR\u2010128\u2010GFP sponge (miR\u2010128 inhibitor). In vitro experiments of cardiac hypertrophy, apoptosis, and aberrant autophagy were performed in cultured cells after Ang II treatment or transfection of miR\u2010128 antagomir. Our results showed that chronic Ang II delivery for 28 days induced cardiac dysfunction, hypertrophy, fibrosis, apoptosis, and oxidative stress in the mice, while the miR\u2010128 expression was notably enhanced in the left ventricle. Silencing miR\u2010128 in the hearts of mice ameliorated Ang II\u2010induced cardiac dysfunction, hypertrophy, fibrosis apoptosis, and oxidative stress injury. Moreover, Ang II induced excessive autophagy in the mouse hearts, which was suppressed by miR\u2010128 knockdown. In cultured cells, Ang II treatment induced a marked elevation in the miR\u2010128 expression. Downregulation of miR\u2010128 in the cells by transfection with miR\u2010128 antagomir attenuated Ang II\u2010induced apoptosis and oxidative injury probably via directly targeting on the SIRT1\/p53 pathway. Intriguingly, we found that miR\u2010128 inhibition activated PIK3R1\/Akt\/mTOR pathway and thereby significantly damped Ang II\u2010stimulated pathological autophagy in cardiomyocytes, which consequently mitigated cell oxidative stress and apoptosis. In conclusion, downregulation of miR\u2010128 ameliorates Ang II\u2010provoked cardiac oxidative stress, hypertrophy, fibrosis, apoptosis, and dysfunction in mice, likely through targeting on PIK3R1\/Akt\/mTORC1 and\/or SIRT1\/p53 pathways. These results indicate that miR\u2010128 inhibition might be a potent therapeutic strategy for maladaptive cardiac remodeling and heart failure.<\/jats:p>","DOI":"10.1155\/2021\/8889195","type":"journal-article","created":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T22:35:23Z","timestamp":1633386923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Downregulation of miR\u2010128 Ameliorates Ang II\u2010Induced Cardiac Remodeling via SIRT1\/PIK3R1 Multiple Targets"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4424-3349","authenticated-orcid":false,"given":"Heqin","family":"Zhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingli","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xumeng","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaina","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WenZhuo","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0421-2046","authenticated-orcid":false,"given":"Zhenghang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,4]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00395.2018"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00059-019-4819-2"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-017-9756-y"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2020.03.007"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.036146"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S156810"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.20452\/pamw.15137"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2020.04.032"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2019.00065"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03019-z"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5208"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.11.029"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.79.2.163"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.17-650"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13519"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0515-4"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.12.003"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104276"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20170982"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14468"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.3892\/or.2015.3936"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00775"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.7868\/S0026898415010061"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2018-0207"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28025"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-019-0074-5"},{"key":"e_1_2_11_27_2","first-page":"2757","article-title":"AMPK regulates energy metabolism through the SIRT1 signaling pathway to improve myocardial hypertrophy","volume":"22","author":"Dong H. 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