{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T13:16:14Z","timestamp":1775308574277,"version":"3.50.1"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,7,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In cardiac hypertrophy and failure, there is a widespread alteration in\n              <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n              splicing, but the role of splice variants in cardiac hypertrophy has not yet been fully elucidated. In this study, we used an exon array to identify novel splice variants associated with cardiac hypertrophy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We performed genome\u2010wide exon array analysis and developed a splicing profile in murine hearts with hypertrophy induced by transverse aortic constriction for 8\u00a0weeks. Following global analysis of splice variants using the Mouse Exon 1.0\n              <jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content>\n              Array, we identified 46 spliced genes and narrowed our focus to 1 gene, mitochondrial tumor suppressor 1 (\n              <jats:italic>Mtus1<\/jats:italic>\n              ), whose splice variants were registered in the\n              <jats:styled-content style=\"fixed-case\">NCBI<\/jats:styled-content>\n              RefSeq database. Notably, one of the splice variants\n              <jats:italic>Mtus1A<\/jats:italic>\n              was specifically upregulated, although the total expression of the\n              <jats:italic>Mtus1<\/jats:italic>\n              gene remained unchanged. We showed that Mtus1A was localized in the mitochondria, and its expression level increased with the degree of cardiac hypertrophy. In cultured cardiomyocytes, Mtus1A overexpression reduced phenylephrine\u2010induced reactive oxygen species production and consequent\n              <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\n              phosphorylation, resulting in a decrease in both cell size and protein synthesis. In vivo, cardiac\u2010specific Mtus1A transgenic mice showed left ventricle wall thinning and a reduced hypertrophic response to pressure overload and phenylephrine treatment.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We found that\n              <jats:italic>Mtus1<\/jats:italic>\n              is specifically spliced in hypertrophic hearts and that the Mtus1A variant has an inhibitory effect on cardiac hypertrophy. Mtus1A is, therefore, a possible diagnostic and therapeutic target for cardiac hypertrophy and failure.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.116.003521","type":"journal-article","created":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T01:30:20Z","timestamp":1467855020000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Identification of the Mtus1 Splice Variant as a Novel Inhibitory Factor Against Cardiac Hypertrophy"],"prefix":"10.1161","volume":"5","author":[{"given":"Shin","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Cell Biology, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Asakura","sequence":"additional","affiliation":[{"name":"Department of Clinical Research and Development, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulin","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung\u2010Duk","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Shindo","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Cerebral and Cardiovascular Center, Osaka, 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