2017 Fiscal Year Annual Research Report
Multilateral Research on the Mechanisms of Inherited Arrhythmias
| Project/Area Number |
15H04818
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
堀江 稔 滋賀医科大学, 医学部, 教授 (90183938)
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| Co-Investigator(Kenkyū-buntansha) |
大野 聖子 滋賀医科大学, 学内共同利用施設等, 特任講師 (20610025)
伊藤 英樹 滋賀医科大学, 医学部, 助教 (30402738)
牧山 武 京都大学, 医学研究科, 助教 (30528302)
林 秀樹 滋賀医科大学, 医学部, 非常勤講師 (70464188)
芦原 貴司 滋賀医科大学, 医学部, 講師 (80396259)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 遺伝性不整脈 / 循環器・高血圧 / 遺伝学 / 遺伝子 |
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| Outline of Annual Research Achievements |
電気生理学的な変化を見るためのパッチクランプ法
われわれが、機能解析で従来用いてきた遺伝子組み換え法で作成した変異遺伝子を培養細胞に導入する方法に加えて、健常および疾患特異的なiPS由来心筋細胞も、酵素で単離することによりパッチクランプ法に供することができる。これによりここのイオンチャネルの活性のみならず、活動電位や各イオンチャネル電流変化を詳細に検討した。またiPS由来心筋細胞の場合、自動能を呈する細胞シートの状態で多点平面電極システム（multiple electrode array mapping: MEA）も同時に用いて、多細胞の疑似活動電位を測定し、QT延長症候群の病像との相関を検討した。遺伝子変異の同定に次世代シークエンサーをつかうことにより、より広範囲な遺伝子異常を発見することになってきており、これらの方法論には機能解析がより重要となりつつある。（担当：牧山、伊藤、大野、林、堀江）
コンピュータシュミレーションを多面的に活用したシステムバイオロジーへの展開
生命体としてのヒトの中では。上記のような多様な方法で観察された生理あるいは病的現象は、ひとるのシステムとして働いている。これらを統合的に解析するには、コンピュータが絶大な威力を発揮する。分担研究者の芦原らは、当該分野の専門家であり、とくに不整脈のバイドメイン・モデルを用いたシュミレーションに多くの経験と実績を有している。実験で得られたデータは、綿密に検討し、コンピュータ・モデルに組み込み、疾患発症との関連を検討出来た。（担当：芦原、伊藤、林、堀江）
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| Research Progress Status |
29年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
29年度が最終年度であるため、記入しない。
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[Journal Article] Copy number variations of SCN5A in Brugada syndrome.2018
Author(s)
Sonoda K, Ohno S, Ozawa J, Hayano M, Hattori T, Kobori A, Yahata M, Aburadani I, Watanabe S, Matsumoto Y, Makiyama T, Horie M
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Journal Title
Heart rhythm
Volume: 印刷中
Pages: -
DOI
Peer Reviewed
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[Journal Article] Serum magnesium, phosphorus, and calcium levels and subclinical calcific aortic valve disease: A population-based study.2018
Author(s)
Hisamatsu T, Miura K, Fujiyoshi A, Kadota A, Miyagawa N, Satoh A, Zaid M, Yamamoto T, Horie M, Ueshima H, SESSA Research Group.
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Journal Title
Atherosclerosis
Volume: 印刷中
Pages: -
DOI
Peer Reviewed
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[Journal Article] Impact of ABCB1, ABCG2, and CYP3A5 polymorphisms on plasma trough concentrations of apixaban in Japanese patients with atrial fibrillation.2017
Author(s)
Ueshima S, Hira D, Fujii R, Kimura Y, Tomitsuka C, Yamane T, Tabuchi Y, Ozawa T, Itoh H, Horie M, Terada T, Katsura T
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Journal Title
Pharmacogenetics and genomics
Volume: 27
Pages: 329-336
DOI
Peer Reviewed
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[Journal Article] Development of a Patient-Derived Induced Pluripotent Stem Cell Model for the Investigation of SCN5A-D1275N-Related Cardiac Sodium Channelopathy.2017
Author(s)
Hayano M, Makiyama T, Kamakura T, Watanabe H, Sasaki K, Funakoshi S, Wuriyanghai Y, Nishiuchi S, Harita T, Yamamoto Y, Kohjitani H, Hirose S, Yokoi F, Chen J, Baba O, Horie T, Chonabayashi K, Ohno S, Toyoda F, Yoshida Y, Ono K, Horie M, Kimura T
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Journal Title
Circulation journal : official journal of the Japanese Circulation Society
Volume: 81
Pages: 1783-1791
DOI
Peer Reviewed / Open Access
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[Journal Article] Genotype-Phenotype Correlation of <i>SCN5A</i> Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry.2017
Author(s)
Yamagata K, Horie M, Aiba T, Ogawa S, Aizawa Y, Ohe T, Yamagishi M, Makita N, Sakurada H, Tanaka T, Shimizu A, Hagiwara N, Kishi R, Nakano Y, Takagi M, Makiyama T, Ohno S, Fukuda K, Watanabe H, Morita H, Hayashi K, Kusano K, Kamakura S, Yasuda S, Ogawa H, Miyamoto Y, Kapplinger JD, Ackerman MJ, Shimizu W
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Journal Title
Circulation
Volume: 135
Pages: 2255-2270
DOI
Peer Reviewed
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[Journal Article] Incidence and Prognostic Impact of Heart Failure Hospitalization During Follow-Up After Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction.2017
Author(s)
Taniguchi T, Shiomi H, Morimoto T, Watanabe H, Ono K, Shizuta S, Kato T, Saito N, Kaji S, Ando K, Kadota K, Furukawa Y, Nakagawa Y, Horie M, Kimura T
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Journal Title
The American journal of cardiology
Volume: 119
Pages: 1729-1739
Peer Reviewed
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[Presentation] Novel N-Terminal KCNH2 Mutations Identified in Symptomatic Long QT Syndrome Patients.2017
Author(s)
Fukumoto D, Ohno S, Wada Y, Fujii Y, Ichikawa M, Takayama K, Fukuyama M, Itoh H, Ding WG, Matsuura H, Horie M
Organizer
APHRS2017
Int'l Joint Research
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[Presentation] Modelling Long-QT Syndrome Type 3 Associated with Near-Miss Sudden Infant Death Syndrome Using Human-Induced Pluripotent Stem Cells.2017
Author(s)
Hirose S, Makiyama T, Melgari D, Wu J, Yokoi F, Wuriyanghai Y, Kohjitani H, Yamamoto Y, Nishiuchi S, Hayano M, Harita T, Yoshimoto J, Ohno S, Yoshida Y, Horie M, Kimura T
Organizer
APHRS2017
Int'l Joint Research
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[Presentation] KCNJ3 N496H A Rare Variant in Japanese as a Cause of Susceptible Gene for Ventricular Fibrillation in Overlap Syndromes between LQT and CPVT.2017
Author(s)
Aiba T, Ohno S, Ono M, Shigemizu D, Toyoda F, Miake J, Hagiwara A, Shinohara T, Okumura S, Toda T, Satake W, Tsunoda T, Shimamoto K, Sekine A, Takahashi A, Miyamoto Y, Tanaka T, Kusano K, Horie M, Shimizu W.
Organizer
APHRS2017
Int'l Joint Research
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[Presentation] Gene-Based Risk Stratification for Cardiac Disorders in LMNA Mutation Carriers.2017
Author(s)
Nishiuchi S, Makiyama T, Aiba T, Nakajima K, Ishikawa T, Murakoshi N, Watanabe H, Ohno S, Doi T, Shizuta S, Minamino T, Saito Y, Oginosawa Y, Nogami A, Aonuma K, Kusano K, Makita N, Shimizu W, Horie M, Kimura T
Organizer
APHRS2017
Int'l Joint Research
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[Presentation] lL-cis-Diltiazem Ameliorates Impaired Calcium Channel Inactivation in a Patient-Specific Stem Cell Model of Long-QT Syndrome with a Calmodulin Mutation.2017
Author(s)
Yokoi F, Makiyama T, Harita T, Yamamoto Y, Hayano M, Nishiuchi S, Kohjitani H, Wuriyanghai Y, Hirose S, Toyoda F, Yoshida Y, Makita N、Horie M, Kimura T
Organizer
APHRS2017
Int'l Joint Research
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[Presentation] Drug-Induced Long QT Syndrome in a Patient with an ANK2 Mutation.2017
Author(s)
Kyodo A, Sakatani T, Shimoo S, Takamatsu K, Tsuji Y, Mera K, Koide M, Isodono K, Tsubakimoto Y, Matsuo A, Inoue K, Fujita H, Ichikawa M, Ohno S, Horie M
Organizer
APHRS2017.
Int'l Joint Research
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[Presentation] ex Dependent Risk of Sudden Death or Sick Sinus Syndrome in a Family with Brugada Syndrome.2017
Author(s)
Aizawa Y, Fujisawa T, Katsumata Y, Ohno S, Sonoda K, Hayashi H, Hojo R, Fukamizu S, Nakajima K, Kunitomi A, Nishiyama T, Kimura T, Nishiyama N, Kurita Y, Takatsuki S, Ogwa S, Kosaki K, Nakazato Y, Horie M, Fukuda K
Organizer
APHRS2017.
Int'l Joint Research
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[Presentation] Is Cardiac Resynchronization Therapy Able to Improve Mortality of Heart Failure in Patients with Laminopathy?2017
Author(s)
Nakajima K, Aiba T, Nishiuchi S, Makiyama T, Onoue K, Kamakura T, Wada M, Ishibashi K, Inoue Y, Miyamoto K, Okamura H, Nagase S, Noda T, Ohno S, Miyamoto Y, Saito Y, Horie M, Kimura T, Shimizu W, Kusano K.
Organizer
APHRS2017
Int'l Joint Research
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[Presentation] CALM2-D134H Mutation Associated with Long-QT Syndrome Prevents Inactivation of L-type Ca2+ Currents in Human iPS Cell Derived Cardiomyocytes.2017
Author(s)
Yamamoto Y, Makiyama T, Harita T, Hayano M, Nishiuchi S, Wuriyanghai Y, Kohjitani H, Hirose S, Yokoi F, Ishikawa T, Ohno S, Chinabayashi K, Suda K, Yoshida Y, Horie M, Makita N, Kimura T.
Organizer
APHRS2017
Int'l Joint Research
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[Presentation] Human iPSC-Derived Myocyte Mmodel of SCN5A-D1275N-Related Cardiac Sodium Channelopathy Reveals Diminished Sodium Currents Resulting From Enhanced Protein Degradation.2017
Author(s)
Hayano M,Makiyama T, Kamakura T, Watanabe H, Sasaki K, Funakoshi S, Wuriyanghai Y, Nishiguchi S, Harita T, Yamamoto Y,.Kohjitani H, Hirose S, Yokoi F, Chen J, Baba O, Horie T, Chonabayahi K, Ohno S, Toyoda F, Yoshida Y, Ohno K, Horie M, Kimura T.
Organizer
AHA2017
Int'l Joint Research
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[Presentation] CALM2-D134H Mutation Associated with Long-QT Syndrome Delayed Inactivation of L-type Ca2+ Currents in Human iPS Cells Derived Cardiomyocytes.2017
Author(s)
Yamamoto Y, Makiyama T, Harita T, Hayano M, Suguru N, Wuriyanghai Y, Kohjitani H, Hirose S, Yokoi F, Ishikawa T, Ohno S, Chonabayashi K, Suda K, Yoshida Y, Horie M, Makita N, Kimura T.
Organizer
AHA2017
Int'l Joint Research
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[Presentation] Propranolol Inhibits Late Sodium Current in Long-QT Syndrome Type 3 Human Induced Pluripotent Stem Cell-drived Myocyte Model.2017
Author(s)
irose S, Makiyama T, Melgari D, Wu J, Yokoi F, Wuriyanghai Y, Yamamoto Y, Kohjitani H, Nishiguchi S, Harita T, Hayano M, Yoshimoto J, Ohno S, Yoshida Y, Horie M, Kimura T.
Organizer
AHA2017
Int'l Joint Research
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[Presentation] Novel Mathematical Modeling of Human Induced Pluripotent Stem Cell Derived Cardiomyocyte can Recapitulate Action Potentials of All Subtypes Including Nodal Like Cells, and Reproduced Drug Testing and Gene Mutation Model Accurately.2017
Author(s)
Kohjitani K, Kouda S, Himeno Y, Makiyama T, Hirose S, Wuriyanghai Y, Yamamoto Y, Horie M, Kimura T, Noma A, Amano A.
Organizer
AHA2017
Int'l Joint Research
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[Presentation] Analyzing vectorcardiograms synthesized from 12-lead electrocardiogram to predict the origin of sinus rhythm and premature contraction.2017
Author(s)
Inada S, Inoue Y, Shibata N, Yamamoto T, Ashihara T, Aiba T, Kusano K, Ikeda T, Mitsui K, Nakazawa K
Organizer
ICE, ISHNE
Int'l Joint Research
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