{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T18:51:26Z","timestamp":1777402286331,"version":"3.51.4"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2013,9,26]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Sudden cardiac death due to malignant ventricular arrhythmia is a devastating manifestation of cardiac hypertrophy. Sarcomere protein myosin binding protein C is functionally related to cardiac diastolic function and hypertrophy. Zebrafish is a better model to study human electrophysiology and arrhythmia than rodents because of the electrophysiological characteristics similar to those of humans.<\/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 established a zebrafish model of cardiac hypertrophy and diastolic dysfunction by genetic knockdown of myosin binding protein C gene (\n              <jats:italic>mybpc3<\/jats:italic>\n              ) and investigated the electrophysiological phenotypes in this model. We found expression of zebrafish\n              <jats:italic>mybpc3<\/jats:italic>\n              restrictively in the heart and slow muscle, and\n              <jats:italic>mybpc3<\/jats:italic>\n              gene was evolutionally conservative with sequence homology between zebrafish and human\n              <jats:italic>mybpc3<\/jats:italic>\n              genes. Zebrafish with genetic knockdown of\n              <jats:italic>mybpc3<\/jats:italic>\n              by morpholino showed ventricular hypertrophy with increased myocardial wall thickness and diastolic heart failure, manifesting as decreased ventricular diastolic relaxation velocity, pericardial effusion, and dilatation of the atrium. In terms of electrophysiological phenotypes,\n              <jats:italic>mybpc3<\/jats:italic>\n              knockdown fish had a longer ventricular action potential duration and slower ventricular diastolic calcium reuptake, both of which are typical electrophysiological features in human cardiac hypertrophy and heart failure. Impaired calcium reuptake resulted in increased susceptibility to calcium transient alternans and action potential duration alternans, which have been proved to be central to the genesis of malignant ventricular fibrillation and a sensitive marker of sudden cardiac death.\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              <jats:italic>mybpc3<\/jats:italic>\n              knockdown in zebrafish recapitulated the morphological, mechanical, and electrophysiological phenotypes of human cardiac hypertrophy and diastolic heart failure. Our study also first demonstrated arrhythmogenic cardiac alternans in cardiac hypertrophy.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.113.000231","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T05:13:33Z","timestamp":1379567613000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Inactivation of Myosin Binding Protein C Homolog in Zebrafish as a Model for Human Cardiac Hypertrophy and Diastolic Dysfunction"],"prefix":"10.1161","volume":"2","author":[{"given":"Yau\u2010Hung","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Chemistry, Tamkang University, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiung\u2010Wen","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences, National Yang\u2010Ming University, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu\u2010Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng\u2010Nan","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital Yun\u2010Lin Branch, Yun\u2010Lin, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian\u2010Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fu\u2010Tien","family":"Chiang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of 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