{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:53:41Z","timestamp":1782514421013,"version":"3.54.5"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,1,23]]},"abstract":"\n Background<\/jats:title>\n \n Severe cardiac hypertrophy can lead to cardiac remodeling and even heart failure in the end, which is a leading cause of cardiovascular disease\u2013related mortality worldwide. A disintegrin and metalloprotease\u201022 (\n ADAM<\/jats:styled-content>\n 22), a member of the transmembrane and secreted metalloendopeptidase family, participates in many biological processes, including those in the cardiovascular system. However, there is no explicit information on whether\n ADAM<\/jats:styled-content>\n 22 can regulate the process of cardiac hypertrophy; the effects that\n ADAM<\/jats:styled-content>\n 22 exerts in cardiac hypertrophy remain elusive.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We observed significantly increased\n ADAM<\/jats:styled-content>\n 22 expression in failing hearts from patients with dilated cardiomyopathy and hypertrophic cardiomyopathy; the same trend was observed in mice induced by transaortic constriction and in neonatal rat cardiomyocytes treated by angiotensin\n II<\/jats:styled-content>\n . Therefore, we constructed both cardiac\u2010specific\n ADAM<\/jats:styled-content>\n 22 overexpression and knockout mice. At 4\u00a0weeks after transaortic constriction, cardiac\u2010specific\n ADAM<\/jats:styled-content>\n 22 knockout, by the CRISPR\/Cas9 (clustered regularly interspaced palindromic repeat (CRISPR)\u2013Cas9) system, deteriorated the severity of cardiac hypertrophy in mice, whereas cardiac\u2010specific\n ADAM<\/jats:styled-content>\n 22 overexpression mitigated the degrees of cardiac hypertrophy in mice. Similarly, altered\n ADAM<\/jats:styled-content>\n 22 expression modulated the angiotensin\n II<\/jats:styled-content>\n \u2013mediated cardiomyocyte hypertrophy in neonatal rat cardiomyocytes. After screening several signaling pathways, we found\n ADAM<\/jats:styled-content>\n 22 played a role in inhibition of protein kinase B (\n AKT<\/jats:styled-content>\n ) activation. Under the cardiac\u2010specific\n ADAM<\/jats:styled-content>\n 22 knockout background,\n AKT<\/jats:styled-content>\n activation was enhanced in transaortic constriction\u2013induced mice and angiotensin\n II<\/jats:styled-content>\n \u2013stimulated neonatal rat cardiomyocytes, with a severe degree of cardiac hypertrophy. Treatment of a specific\n AKT<\/jats:styled-content>\n inhibitor attenuated the transaortic constriction\u2013enhanced\n AKT<\/jats:styled-content>\n activation and cardiac hypertrophy in mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The findings demonstrated that\n ADAM<\/jats:styled-content>\n 22 negatively regulates the\n AKT<\/jats:styled-content>\n activation and the process of cardiac hypertrophy and may provide new insights into the pathobiological features of cardiac hypertrophy.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.005696","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T20:10:55Z","timestamp":1516651855000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["A Disintegrin and Metalloprotease\u201022 Attenuates Hypertrophic Remodeling in Mice Through Inhibition of the Protein Kinase B Signaling Pathway"],"prefix":"10.1161","volume":"7","author":[{"given":"Lingyun","family":"Ren","sequence":"first","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuangyan","family":"Wu","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Yang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Chen","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ye","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Huang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Deng","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangchao","family":"Ding","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manhua","family":"Chen","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahong","family":"Xia","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.yjmcc.2016.06.001","article-title":"Physiological and pathological cardiac hypertrophy","volume":"97","author":"Shimizu I","year":"2016","unstructured":"Shimizu I, Minamino T. 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