{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:37:34Z","timestamp":1790671054326,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T00:00:00Z","timestamp":1505865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570208"],"award-info":[{"award-number":["81570208"]}],"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":["81670206"],"award-info":[{"award-number":["81670206"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>Recently, <jats:italic>PSEN1<\/jats:italic> has been reported to have mutations in dilated cardiomyopathy pedigrees. However, the function and mechanism of <jats:italic>PSEN1<\/jats:italic> in cardiomyopathy remains unresolved. Here, we established four types of genetically modified mice to determine the function of <jats:italic>PSEN1<\/jats:italic> in cardiac development and pathology. <jats:italic>PSEN1<\/jats:italic> null mutation resulted in perinatal death, retardation of heart growth, ventricular dilatation, septum defects, and valvular thickening. <jats:italic>PSEN1<\/jats:italic> knockout in adults led to decreased muscle fibers, widened sarcomere Z lines and reduced lengths of sarcomeres in cardiomyocytes. Cardiovascular loss of function of <jats:italic>PSEN1<\/jats:italic> induced by <jats:italic>Sm22a\u2010Cre<\/jats:italic> or <jats:italic>Myh6\u2010Cre\/ER<\/jats:italic>\/tamoxifen also resulted in severe ultrastructural abnormalities, such as relaxed gap junctions between neighboring cardiomyocytes. Functionally, cardiovascular deletion of <jats:italic>PSEN1<\/jats:italic> caused spontaneous mortality from birth to adulthood and led to diastolic heart dysfunction, including decreased volume of the left ventricle at the end\u2010systolic and end\u2010diastolic stages. Additionally, in a myocardial ischemia model, deletion of <jats:italic>PSEN1<\/jats:italic> in the cardiovascular system first protected mice by inducing adaptive hypertrophy but ultimately resulted in severe heart failure. Furthermore, a collection of genes was abnormally expressed in the hearts of cardiac\u2010specific <jats:italic>PSEN1<\/jats:italic> knockout mice. They were enriched in cell proliferation, calcium regulation, and so on. Taken together, dynamic regulation and abnormal function of <jats:italic>PSEN1<\/jats:italic> underlie the pathogenesis of cardiovascular diseases due to ultrastructural abnormality of cardiomyocytes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.26057","type":"journal-article","created":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T21:26:00Z","timestamp":1497561960000},"page":"1548-1557","source":"Crossref","is-referenced-by-count":8,"title":["Conditionally targeted deletion of <i>PSEN1<\/i> leads to diastolic heart dysfunction"],"prefix":"10.1002","volume":"233","author":[{"given":"Xiao\u2010Wei","family":"Song","sequence":"first","affiliation":[{"name":"Department of Biophysics Second Military Medical University Shanghai China"},{"name":"Department of Cardiology Changhai Hospital Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing\u2010Ning","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Biophysics Second Military 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