Deciphering cardiovascular diseases by disease models

• Project/Area Number: 16H05304
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Keio University
• Principal Investigator: Yuasa Shinsuke 慶應義塾大学, 医学部(信濃町), 講師 (90398628)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 循環器 / 心臓 / 疾患モデル / 疾患解析 / 遺伝子 / 病態解明

Outline of Final Research Achievements

We established novel disease models in vitro and in vivo. We have searched for the molecular mechanism by carrying out comprehensive gene expression analysis for cells and tissues in various models. Through these analyses, we established a new concept of disease mechanism and develop the novel drug screening systems.

Academic Significance and Societal Importance of the Research Achievements

循環器疾患は世界中で未だ罹患患者数が極めて多く、有効な内科的治療方法が限られている。さらに近年は治療方法の開発に向けた研究も限られており、研究手法そのものから革新が期待されている。本研究においては、循環器疾患の病態解明研究や創薬に向けた基盤技術として用いられる事が期待されている。

Research Products

• [Journal Article] Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension (2020)
  • Author(s): Hiraide Takahiro、Kataoka Masaharu、Suzuki Hisato、Aimi Yuki、Chiba Tomohiro、Isobe Sarasa、Katsumata Yoshinori、Goto Shinichi、Kanekura Kohsuke et al.,
  • Journal Title: The Journal of Heart and Lung Transplantation Volume: 39 Issue: 2 Pages: 103-112
  • DOI: 10.1016/j.healun.2019.08.022
  • Peer Reviewed
• [Journal Article] Stem Cell Aging in Skeletal Muscle Regeneration and Disease (2020)
  • Author(s): Yamakawa Hiroyuki、Kusumoto Dai、Hashimoto Hisayuki、Yuasa Shinsuke
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 5 Pages: 1830-1830
  • DOI: 10.3390/ijms21051830
  • Peer Reviewed / Open Access
• [Journal Article] The application of convolutional neural network to stem cell biology. (2019)
  • Author(s): Kusumoto D, Yuasa S
  • Journal Title: Inflamm Regen. Volume: 39 Issue: 1
  • DOI: 10.1186/s41232-019-0103-3
  • Peer Reviewed / Open Access
• [Journal Article] Discrepancy between patient-reported quality of life and the prognostic assessment of Japanese patients hospitalized with acute heart failure (2019)
  • Author(s): Shoji Satoshi、Shiraishi Yasuyuki、Sawano Mitsuaki、Katsumata Yoshinori、Yuasa Shinsuke、Kohno Takashi、Fukuda Keiichi、Spertus John A.、Kohsaka Shun
  • Journal Title: Heart and Vessels Volume: 印刷中 Issue: 9 Pages: 1464-1470
  • DOI: 10.1007/s00380-019-01378-1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A tale of two sisters with hypertrophic cardiomyopathy and recurrent embolism: When is the optimal timing of the intervention for left atrial appendage? (2019)
  • Author(s): Kimura Mai、Kohno Takashi、Makino Shinji、Okuda Shigeo、Nawata Kan、Yanagisawa Ryo、Kojima Hidenori、Nishiyama Takahiko、Aizawa Yoshiyasu、Yuasa Shinsuke、Murata Mitsushige、Maekawa Yuichiro、Okamoto Kazuma、Shimizu Hideyuki、Fukuda Keiichi
  • Journal Title: Heart & Lung Volume: 48 Issue: 3 Pages: 198-200
  • DOI: 10.1016/j.hrtlng.2018.08.010
  • Peer Reviewed / Open Access
• [Journal Article] Shortening Hospital Stay Is Feasible and Safe in Patients With Chronic Thromboembolic Pulmonary Hypertension Treated With Balloon Pulmonary Angioplasty (2019)
  • Author(s): Kimura Mai、Kohno Takashi、Kawakami Takashi、Kataoka Masaharu、Hiraide Takahiro、Moriyama Hidenori、Isobe Sarasa、Tsugu Toshimitsu、Itabashi Yuji、Murata Mitsushige、Yuasa Shinsuke、Fukuda Keiichi
  • Journal Title: Canadian Journal of Cardiology Volume: 35 Issue: 2 Pages: 193-198
  • DOI: 10.1016/j.cjca.2018.12.001
  • Peer Reviewed
• [Journal Article] Excessive Daytime Sleepiness Is Associated With Depression Scores, But Not With Sleep-Disordered Breathing in Patients With Cardiovascular Diseases (2018)
  • Author(s): Ohashi M, Kohno T, Kohsaka S, Fukuoka R, Hayashida K, Yuasa S, Sano M, Takatsuki S, Fukuda K.
  • Journal Title: Circulation Journal Volume: 82 Issue: 8 Pages: 2175-2183
  • DOI: 10.1253/circj.CJ-17-1395
  • NAID: 130007419855
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2018-07-25
  • Peer Reviewed
• [Journal Article] Selective modulation of local linkages between active transcription and oxidative demethylation activity shapes cardiomyocyte-specific gene-body epigenetic status in mice. (2018)
  • Author(s): Oda M, Wakabayashi S, Ari Wijetunga N, Yuasa S, Enomoto H, Kaneda R, Yoon SH, Mittal N, Jing Q, Suzuki M, Greally JM, Fukuda K, Makino S
  • Journal Title: BMC genomics Volume: 19 Issue: 1 Pages: 349-349
  • DOI: 10.1186/s12864-018-4752-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prognostic significance of repeated brain natriuretic peptide measurements after percutaneous transluminal septal myocardial ablation in patients with drug-refractory hypertrophic obstructive cardiomyopathy. (2018)
  • Author(s): Akita K, Tsuruta H, Yuasa S, Murata M, Fukuda K, Maekawa Y
  • Journal Title: Open Heart Volume: 5(1) Issue: 1 Pages: e000786-e000786
  • DOI: 10.1136/openhrt-2018-000786
  • Peer Reviewed / Open Access
• [Journal Article] Improvement in the electrocardiograms associated with right ventricular hypertrophy after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension (2018)
  • Author(s): Nishiyama Takahiko、Takatsuki Seiji、Kawakami Takashi、Katsumata Yoshinori、Kimura Takehiro、Kataoka Masaharu、Tsuruta Hikaru、Itabashi Yuji、Murata Mitsushige、Yuasa Shinsuke、Aizawa Yoshiyasu、Fukuda Keiichi
  • Journal Title: IJC Heart & Vasculature Volume: 19 Pages: 75-82
  • DOI: 10.1016/j.ijcha.2018.05.003
  • Peer Reviewed / Open Access
• [Journal Article] Automated Deep Learning-Based System to Identify Endothelial Cells Derived from Induced Pluripotent Stem Cells. (2018)
  • Author(s): Kusumoto D, Lachmann M, Kunihiro T, Yuasa S, Kishino Y, Kimura M, Katsuki T, Itoh S, Seki T, Fukuda K.
  • Journal Title: Stem Cell Reports. Volume: 10(6) Issue: 6 Pages: 1687-1695
  • DOI: 10.1016/j.stemcr.2018.04.007
  • Peer Reviewed
• [Journal Article] Stroke After Percutaneous Coronary Intervention in the Era of Transradial Intervention. (2018)
  • Author(s): Shoji S, Kohsaka S, Kumamaru H, Sawano M, Shiraishi Y, Ueda I, Noma S, Suzuki M, Numasawa Y, Hayashida K, Yuasa S, Miyata H, Fukuda K.
  • Journal Title: Circ Cardiovasc Interv. Volume: 11(12) Issue: 12
  • DOI: 10.1161/circinterventions.118.006761
  • Peer Reviewed
• [Journal Article] Automated Deep Learning-Based System to Identify Endothelial Cells Derived from Induced Pluripotent Stem Cells. (2018)
  • Author(s): Kusumoto D, Lachmann M, Kunihiro T, Yuasa S, Kishino Y, Kimura M, Katsuki T, Itoh S, Seki T, Fukuda K
  • Journal Title: Stem Cell Reports. Volume: 10(6) Issue: 5 Pages: 1687-1695
  • DOI: 10.1161/circresaha.119.314678
  • Peer Reviewed
• [Journal Article] Patient confidence regarding secondary lifestyle modification and knowledge of 'heart attack' symptoms following percutaneous revascularisation in Japan: a cross-sectional study. (2018)
  • Author(s): Kitakata H, Kohno T, Kohsaka S, Fujino J, Nakano N, Fukuoka R, Yuasa S, Maekawa Y, Fukuda K.
  • Journal Title: BMJ Open. Volume: 8(3) Issue: 3 Pages: e019119-e019119
  • DOI: 10.1136/bmjopen-2017-019119
  • Peer Reviewed / Open Access
• [Journal Article] Percutaneous Occlusion of Patent Ductus Arteriosus for an Elderly Patient With Refractory Congestive Heart Failure. (2018)
  • Author(s): Shoji S, Kanazawa H, Yanagisawa R, Tanaka M, Fukuoka R, Akita K, Kimura M, Arai T, Kawakami T, Hayashida K, Yuasa S, Tsuruta H, Itabashi Y, Murata M, Nishiyama T, Kohno T, Maekawa Y, Fukuda K.
  • Journal Title: Circ Heart Fail. Volume: 2 Issue: 2
  • DOI: 10.1161/circheartfailure.117.004764
  • Peer Reviewed
• [Journal Article] Characteristics and in-hospital outcomes in young patients presenting with acute coronary syndrome treated by percutaneous coronary intervention. (2018)
  • Author(s): Hirota Y, Sawano M, Numasawa Y, Ueda I, Noma S, Suzuki M, Hayashida K, Yuasa S, Maekawa Y, Kohsaka S, Fukuda K.
  • Journal Title: Cardiovasc Interv Ther. Volume: 33(2) Issue: 2 Pages: 154-162
  • DOI: 10.1007/s12928-017-0471-z
  • NAID: 40021531353
  • Peer Reviewed
• [Journal Article] Predictors of high cost after percutaneous coronary intervention: A review from Japanese multicenter registry overviewing the influence of procedural complications. (2017)
  • Author(s): Inohara T, Numasawa Y, Higashi T, Ueda I, Suzuki M, Hayashida K, Yuasa S, Maekawa Y, Fukuda K, Kohsaka S.
  • Journal Title: Am Heart J. Volume: 194 Pages: 61-72
  • DOI: 10.1016/j.ahj.2017.08.008
  • Peer Reviewed
• [Journal Article] Flecainide ameliorates arrhythmogenicity through NCX flux in Andersen-Tawil syndrome-iPS cell-derived cardiomyocytes. (2017)
  • Author(s): Kuroda Y, Yuasa S, Watanabe Y, Ito S, Egashira T, ・・・Horie M, Kamiya K, Fukuda K.
  • Journal Title: Biochemistry and Biophysics Reports Volume: 9 Pages: 245-256
  • DOI: 10.1016/j.bbrep.2017.01.002
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic barrier against the propagation of fluctuating gene expression in embryonic stem cells. (2017)
  • Author(s): Saito Y, Kunitomi A, Seki T, Tohyama S, Kusumoto D, Takei M, Kashimura S, Hashimoto H, Yozu G, Motoda C, Shimojima M, Egashira T, Oda M, Fukuda K, Yuasa S.
  • Journal Title: FEBS Lett. Volume: 591(18) Issue: 18 Pages: 2879-2889
  • DOI: 10.1002/1873-3468.12791
  • Peer Reviewed
• [Journal Article] Barriers Associated With Door-to-Balloon Delay in Contemporary Japanese Practice (2017)
  • Author(s): Ikemura N, Sawano M, Shiraishi Y, Ueda I, Miyata H, Numasawa Y, Noma S, Suzuki M, Momiyama Y, Inohara T, Hayashida K, Yuasa S, Maekawa Y, Fukuda K, Kohsaka S.
  • Journal Title: Circulation Journal Volume: 81 Issue: 6 Pages: 815-822
  • DOI: 10.1253/circj.CJ-16-0905
  • NAID: 130005679702
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient. (2017)
  • Author(s): Shimojima M, Yuasa S, Motoda C, Yozu G, Nagai T, Ito S, Lachmann M, Kashimura S, Takei M, Kusumoto D, Kunitomi A, Hayashiji N, Seki T, Tohyama S, Hashimoto H, Kodaira M, Egashira T, Hayashi K, Nakanishi C, Sakata K, Yamagishi M, Fukuda K.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 44312-44312
  • DOI: 10.1038/srep44312
  • NAID: 120006325351
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nocturnal intermittent hypoxia and short sleep duration are independently associated with elevated C-reactive protein levels in patients with coronary artery disease. (2017)
  • Author(s): Fukuoka R, Kohno T, Kohsaka S, Yanagisawa R, Kawakami T, Hayashida K, Kanazawa H, Yuasa S, Maekawa Y, Sano M, Fukuda K.
  • Journal Title: Sleep Med. Volume: 29 Pages: 29-34
  • DOI: 10.1016/j.sleep.2016.09.012
  • Peer Reviewed
• [Journal Article] An RyR2 mutation found in a family with a short-coupled variant of torsade de pointes. (2017)
  • Author(s): Kimura M, Fujisawa T, Aizawa Y, Matsuhashi N, Ito S, Nakajima K, Kashimura S, Kunitomi A, Katsumata Y, Nishiyama T, Kimura T, Nishiyama N, Yuasa S, Takatsuki S, Kosaki K, Fukuda K.
  • Journal Title: Int J Cardiol. Volume: 227 Pages: 367-369
  • Peer Reviewed
• [Journal Article] Partial IK1 blockade destabilizes spiral wave rotation center without inducing wave breakup and facilitates termination of reentrant arrhythmias in ventricles (2016)
  • Author(s): Kushiyama Y, Honjo H, Niwa R, Takanari H, Yamazaki M, Takemoto Y, Sakuma I, Kodama I, Kamiya K
  • Journal Title: American Journal of Physiology Heart and Circulatory Physiology Volume: 311 Issue: 1 Pages: 750-758
  • DOI: 10.1038/srep34198
  • NAID: 120005946586
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Significant reduction of left atrial volume concomitant with clinical improvement after percutaneous transluminal septal myocardial ablation for drug-refractory hypertrophic obstructive cardiomyopathy, and its precise detection with multidetector CT (2016)
  • Author(s): Maekawa Y, Akita K, Tsuruta H, Yamada Y,Hayashida K, Yuasa S, Murata M, Jinzaki M, Fukuda K
  • Journal Title: Open Heart Volume: 3 Issue: 1 Pages: 1-8
  • DOI: 10.1136/openhrt-2015-000359
  • Peer Reviewed / Open Access
• [Journal Article] H1foo Has a Pivotal Role in Qualifying Induced Pluripotent Stem Cells (2016)
  • Author(s): Kunitomi A, Yuasa S, Sugiyama F, Saito Y, Seki T, Kusumoto D, Kashimura S, Takei M, Tohyama S, Hashimoto H, Egashira T, Tanimoto Y, Mizuno S, Tanaka S, Okuno H, Yamazawa K, Watanabe H, Oda M, Kaneda R, Matsuzaki Y, Nagai T, Okano H, Yagami K, Tanaka M, Fukuda K.
  • Journal Title: Stem Cell Reports Volume: 6 Issue: 6 Pages: 825-833
  • DOI: 10.1016/j.stemcr.2016.04.015
  • NAID: 120007135348
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intensive statin therapy stabilizes C-reactive protein, but not chemokine in stable coronary artery disease treated with an everolimus-eluting stent (2016)
  • Author(s): Sukegawa H., Abe, T. et al.
  • Journal Title: Coronary Artery Disease Volume: 27 Issue: 5 Pages: 405-411
  • DOI: 10.1097/mca.0000000000000375
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells. (2016)
  • Author(s): Tohyama S, Fujita J, Hishiki T, Matsuura T, Hattori F, Ohno R, Kanazawa H, Seki T, Nakajima K, Kishino Y, Okada M, Hirano A, Kuroda T, Yasuda S, Sato Y, Yuasa S, Sano M, Suematsu M, Fukuda K.
  • Journal Title: Cell Metab Volume: 23 Issue: 4 Pages: 663-74
  • DOI: 10.1016/j.cmet.2016.03.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Arrhythmogenic disease modeling using iPS cells (2018)
  • Author(s): Shinsuke Yuasa
  • Organizer: The 1st JCS Council Forum on Basic CardioVascular Research
  • Invited
• [Presentation] iPS細胞を用いた心不全の診断 (2017)
  • Author(s): 湯浅慎介
  • Organizer: 日本心不全学会
  • Invited
• [Presentation] Cardiac Arrhythmia Modeling by Induced Pluripotent Stem Cells (2017)
  • Author(s): Shinsuke Yuasa
  • Organizer: The 10th Asia Pacific Heart Rhythm Society Scientific Session In Conjunction with the Annual Meeting of the Japanese Heart Rhythm Society
  • Invited
• [Presentation] Disease modeling by iPS cells (2017)
  • Author(s): Shinsuke Yuasa
  • Organizer: The 10th Asia Pacific Heart Rhythm Society Scientific Session In Conjunction with the Annual Meeting of the Japanese Heart Rhythm Society
  • Invited
• [Presentation] iPS細胞を用いた循環器疾患の病態解明 (2017)
  • Author(s): 湯浅慎介
  • Organizer: 日本炎症・再生医学会
  • Invited
• [Presentation] iPS細胞を用いた心筋症の病態解明 (2017)
  • Author(s): 湯浅慎介
  • Organizer: 第3回 日本心筋症研究会
  • Invited
• [Presentation] Arrhythmogenic Disease Modeling by iPS Cells. (2017)
  • Author(s): 湯浅慎介
  • Organizer: The 81st Annual Scientific Meeting of the Japanese Circulation Society.
  • Invited
• [Presentation] iPS細胞を用いた肥大型心筋症の治療方法の開発 (2016)
  • Author(s): 湯浅慎介
  • Organizer: 第20回日本心不全学会
  • Invited
• [Presentation] G-CSFによる骨格筋幹細胞維持機構と筋疾患治療への応用 (2016)
  • Author(s): 湯浅慎介
  • Organizer: 第89回日本生化学会大会
  • Invited
• [Presentation] iPS細胞を用いた循環器疾患の解析 (2016)
  • Author(s): 湯浅慎介
  • Organizer: 第37回日本炎症・再生医学会
  • Invited