Arimura T., Muchir A., Kuwahara M., Morimoto S., Ishikawa T., Du C.K., Zhan D.Y., Nakao S., Machida N., Tanaka R., Yamane Y., Hayashi T., Kimura A. . Overexpression of heart-specific small sub2017 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： American Journal of Physiology - Heart and Circulatory Physiology Mutations in genes encoding components of the sarcomere cause cardiomyopathy, which is often associated with abnormal Ca2+ sensitivity of muscle contraction. We have previously shown that a heartspecific myosin light chain phosphatase small subunit (hHS-M21) increases the Ca2+ sensitivity of muscle contraction. The aim of the present study was to investigate the function of hHS-M21 in vivo and the causative role of abnormal Ca2+ sensitivity in cardiomyopathy. We generated transgenic mice with cardiac-specific overexpression of hHS-M21. We confirmed that hHS-M21 increased the Ca2+ sensitivity of cardiac muscle contraction in vivo, which was not followed by an increased phosphorylation of myosin light chain 2 isoforms. hHS-M21 transgenic mice developed severe systolic dysfunction with myocardial fibrosis and degeneration of cardiomyocytes in association with sinus bradycardia and atrioventricular conduction defect. The contractile dysfunction and cardiac fibrosis were improved by treatment with the Rho kinase inhibitor fasudil. Our findings suggested that the overexpression of hHS-M21 results in cardiac dysfunction and conduction disturbance via non-myosin light chain 2 phosphorylationdependent regulation. NEW & NOTEWORTHY The present study is the first to develop mice with transgenic overexpression of a heart-specific myosin light chain phosphatase small subunit (hHS-M21) and to examine the effects of hHS-M21 on cardiac function. Elevation of hHS-M21 induced heart failure with myocardial fibrosis and degeneration of cardiomyocytes accompanied by supraventricular arrhythmias. DOI： 10.1152/ajpheart.00696.2017 Scopus PubMed researchmap
Kawai H., Morimoto S., Takakuwa Y., Ueda A., Inada K., Sarai M., Arimura T., Mutoh T., Kimura A., Ozaki Y. . Hypertrophic cardiomyopathy accompanied by spinocerebellar atrophy with a novel mut2016 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： International Heart Journal We report the case of a 66 year-old woman with chronic atrial fibrillation, hypertrophic cardiomyopathy (HCM), and spinocerebellar atrophy (SCA). Her mother and first-born son had died of heart disease at the ages of 65 and 16 years, respectively. Four of her 8 siblings had died suddenly of unknown cause or of heart disease, and 2 others of cerebral infarction by the 7th decade. Genetic testing revealed that she had a novel mutation (c. 482C > A, p. Ala161Asp) in the troponin I gene (TNNI3), and no abnormality of the GAA repeat in the frataxin gene. Her older brother with SCA but without HCM was also analyzed, with no abnormality noted in either gene. The Ala161Asp mutation in TNNI3 was implicated in the pathogenesis of her HCM, though an association between HCM and SCA was not revealed. DOI： 10.1536/ihj.15-444 Scopus PubMed CiNii Research researchmap その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J04789&link_issn=&doc_id=20160803160021&doc_link_id=10.1536%2Fihj.15-444&url=https%3A%2F%2Fdoi.org%2F10.1536%2Fihj.15-444&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif
