{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:27:57Z","timestamp":1789464477542,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"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":"publisher","award":["81100087"],"award-info":[{"award-number":["81100087"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570261"],"award-info":[{"award-number":["81570261"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01 HL115195\u201001"],"award-info":[{"award-number":["1R01 HL115195\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Hypertension\u2010induced left ventricular hypertrophy (<jats:styled-content style=\"fixed-case\">LVH<\/jats:styled-content>) is an independent risk factor for heart failure. Regression of <jats:styled-content style=\"fixed-case\">LVH<\/jats:styled-content> has emerged as a major goal in the treatment of hypertensive patients. Here, we tested our hypothesis that the valosin\u2010containing protein (<jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content>), an <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase associate protein, is a novel repressor of cardiomyocyte hypertrophy under the pressure overload stress. Left ventricular hypertrophy (<jats:styled-content style=\"fixed-case\">LVH<\/jats:styled-content>) was determined by echocardiography in 4\u2010month male spontaneously hypertensive rats (<jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>s) vs. age\u2010matched normotensive Wistar Kyoto (<jats:styled-content style=\"fixed-case\">WKY<\/jats:styled-content>) rats. <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content> expression was found to be significantly downregulated in the left ventricle (<jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content>) tissues from <jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>s vs. <jats:styled-content style=\"fixed-case\">WKY<\/jats:styled-content> rats. Pressure overload was induced by transverse aortic constriction (<jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>) in wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) mice. At the end of 2\u00a0weeks, mice with <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content> developed significant <jats:styled-content style=\"fixed-case\">LVH<\/jats:styled-content> whereas the cardiac function remained unchanged. A significant reduction of <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content> at both the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein levels in hypertrophic <jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content> tissue was found in <jats:styled-content style=\"fixed-case\">TAC WT<\/jats:styled-content> mice compared to sham controls. Valosin\u2010containing protein <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content> expression was also observed to be time\u2010 and dose\u2010dependently reduced <jats:italic>in\u00a0vitro<\/jats:italic> in isolated neonatal rat cardiomyocytes upon the treatment of angiotensin <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>. Conversely, transgenic (<jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>) mice with cardiac\u2010specific overexpression of <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content> showed a significant repression in <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">LVH<\/jats:styled-content> vs. litter\u2010matched <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> controls upon 2\u2010week <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>\u2010induced activation of the mechanistic target of rapamycin complex 1 (<jats:styled-content style=\"fixed-case\">mTORC<\/jats:styled-content>1) signaling observed in <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice <jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content>s was also significantly blunted in <jats:styled-content style=\"fixed-case\">VCP TG<\/jats:styled-content> mice. In conclusion, <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content> acts as a novel repressor that is able to prevent cardiomyocyte hypertrophy from pressure overload by modulating the <jats:styled-content style=\"fixed-case\">mTORC<\/jats:styled-content>1 signaling pathway.<\/jats:p>","DOI":"10.1111\/acel.12653","type":"journal-article","created":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T08:22:49Z","timestamp":1502439769000},"page":"1168-1179","source":"Crossref","is-referenced-by-count":25,"title":["The valosin\u2010containing protein is a novel repressor of cardiomyocyte hypertrophy induced by pressure overload"],"prefix":"10.1111","volume":"16","author":[{"given":"Ning","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Division of Physiology Department of Basic Sciences School of Medicine Loma Linda University Loma Linda CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Physiology Department of Basic Sciences School of Medicine Loma Linda University Loma Linda CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaunrick","family":"Stoll","sequence":"additional","affiliation":[{"name":"Division of Physiology Department of Basic Sciences School of Medicine Loma Linda University Loma Linda CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan T.","family":"Hays","sequence":"additional","affiliation":[{"name":"Division of Physiology Department of Basic Sciences School of Medicine Loma Linda University Loma Linda CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Division of Physiology Department of Basic Sciences School of Medicine Loma Linda University Loma Linda CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2010.07.003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2010.04.005"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/2040622312452189"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.08.028"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.6b00350"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.141887"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/00129784-200101040-00005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.845792"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e328340d787"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2017.00021"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1983"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2014.09.004"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21197"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.01.025"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt136"},{"key":"e_1_2_9_17_1","first-page":"1352","article-title":"Effect of telmisartan on the regression of the left ventricular hypertrophy in the patients of essential hypertension","volume":"7","author":"Misra KH","year":"2013","journal-title":"J. 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