{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T19:44:30Z","timestamp":1776109470728,"version":"3.50.1"},"reference-count":31,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiology"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Objectives:&lt;\/i&gt;&lt;\/b&gt; It is known that the expression, activity and alternative splicing of Ca&lt;sup&gt;2+&lt;\/sup&gt;\/calmodulin-dependent protein kinase II\u03b4 (CaMKII\u03b4) are dysregulated in the cardiac remodeling process. Recently, we found a further signaling pathway, by which dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) regulates the alternative splicing of CaMKII\u03b4 via the alternative splicing factor (ASF), i.e. Dyrk1A-ASF-CaMKII\u03b4. In this study, we aimed to investigate whether Dyrk1A-ASF-CaMKII\u03b4 signaling was involved in valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; Rats were subjected to two kidney-one clip (2K1C) surgery and then treated with valsartan (30 mg\/kg\/day) for 8 weeks. Hypertrophic parameter analysis was then performed. Western blot analysis was used to determine the protein expression of Dyrk1A and ASF and RT-PCR was used to analyze the alternative splicing of CaMKII\u03b4 in the left ventricular (LV) sample. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Valsartan attenuated cardiac hypertrophy in 2K1C rats but without impairment of cardiac systolic function. Increased protein expression of Dyrk1A and decreased protein expression of ASF were observed in the LV sample of 2K1C rats. Treatment of 2K1C rats with valsartan reversed the changes in Dyrk1A and ASF expression in the LV sample. Valsartan adjusted the 2K1C-induced imbalance in alternative splicing of CaMKII\u03b4 by upregulating the mRNA expression of CaMKII\u03b4C and downregulating the mRNA expression of CaMKII\u03b4A and CaMKII\u03b4B. &lt;b&gt;&lt;i&gt;Conclusions:&lt;\/i&gt;&lt;\/b&gt; Valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats was mediated, at least partly, by Dyrk1A-ASF-CaMKII\u03b4 signaling.<\/jats:p>","DOI":"10.1159\/000441695","type":"journal-article","created":{"date-parts":[[2015,11,30]],"date-time":"2015-11-30T22:01:18Z","timestamp":1448920878000},"page":"198-204","source":"Crossref","is-referenced-by-count":8,"title":["Dyrk1A-ASF-CaMKII\u03b4 Signaling Is Involved in Valsartan Inhibition of Cardiac Hypertrophy in Renovascular Hypertensive Rats"],"prefix":"10.1159","volume":"133","author":[{"given":"Jian","family":"Yao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaotong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6803-1776","authenticated-orcid":false,"given":"Hongzhuan","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2015,12,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2013.04.018"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.06.007"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000069686.31472.C5"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108525200"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.11.036"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802645200"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1999.5998"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.006759"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr023"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2015.05.015"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1038\/jhh.2011.91"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-010-0039-1"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.09336FP"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24445"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-009-0043-1"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e31827a0278"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.22.1"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1983"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1161\/hy1201.101214"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1177\/1470320308096048"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.239749"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.01.012"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813013106"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e3181e1d263"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20020780"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00015"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1038\/nature04678"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1161\/hh0901.091204"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.32.1.78"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/141039"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-006-0040-9"}],"container-title":["Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/441695","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/441695","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/441695","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T18:03:09Z","timestamp":1745431389000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000441695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,1]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2016,2,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000441695","archive":["Portico"],"relation":{},"ISSN":["0008-6312","1421-9751"],"issn-type":[{"value":"0008-6312","type":"print"},{"value":"1421-9751","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,1]]}}}