心不全発症における心筋細胞不均一性の意義

2019 Fiscal Year Annual Research Report

• Project/Area Number: 17H01560
• Research Institution: The University of Tokyo
• Principal Investigator: 小室 一成 東京大学, 医学部附属病院, 教授 (30260483)
• Co-Investigator(Kenkyū-buntansha): 野村 征太郎 東京大学, 医学部附属病院, 特任助教 (10722118) ; 波多野 将 東京大学, 医学部附属病院, 特任准教授 (20456130) ; 東口 治弘 東京大学, 医学部附属病院, 特任准教授 (40436358)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 心不全 / シングルセル解析 / 不均一性

Outline of Annual Research Achievements

１）1 細胞メカニカルストレス応答定量解析法（生体１細胞RNA-seq解析法）の確立と応用：シングルセルRNA-seq情報から重要な細胞間相互作用を抽出する技術を確立し、心筋・非心筋細胞の間の相互作用を包括的に解析した。その結果、心臓線維芽細胞から心筋細胞へと誘導されるTGF-betaシグナルが心筋細胞の老化を誘導していることを明らかにし、心筋細胞老化の特異的な分泌形質を解明することに成功した。２）1 細胞メカニカルストレス応答in situ定量解析法（生体１分子RNA FISH法）の確立と応用：１分子RNA FISH法とIn Cell Analyzer6000の統合によるハイスループットイメージングにより生体1分子RNA FISH法を確立し、解剖学的特徴と関係する遺伝子発現パターンを詳細に解析し、圧負荷心不全モデルにおける空間的な遺伝子発現の不均一性を詳細に明らかにした。３）非心筋細胞の１細胞RNA-seq解析：心不全過程における非心筋細胞の一細胞遺伝子発現解析により、線維芽細胞における未知の遺伝子マーカーを同定し、その遺伝子改変マウスの心臓機能解析・シングルセル解析を行った。これにより心臓線維芽細胞の活性化に伴う分子メカニズムの解明に成功した。４）ヒト心不全患者の１細胞遺伝子発現解析：心不全患者の心臓シングルセル解析技術を確立して患者の病態特異的な遺伝子発現パターンおよび分子マーカー（DNA損傷応答シグナル）を同定した。そして分子病理解析により、このマーカーを用いた心不全層別化が可能であることを実証した。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Serum uric acid level and subclinical left ventricular dysfunction: a community-based cohort study. (2020)
  • Author(s): Nakanishi K, Daimon M, Yoshida Y, Ishiwata J, Sawada N, Hirokawa M, Kaneko H, Nakao T, Mizuno Y, Morita H, Di Tullio MR, Homma S, Komuro I.
  • Journal Title: ESC Heart Fail. Volume: - Pages: -
  • DOI: 10.1002/ehf2.12691.
  • Peer Reviewed / Open Access
• [Journal Article] Estrogen Receptor-α Non-Nuclear Signaling Confers Cardioprotection and Is Essential to cGMP-PDE5 Inhibition Efficacy. (2020)
  • Author(s): Fukuma N, Takimoto E, Ueda K, Liu P, Tajima M, Otsu Y, Kariya T, Harada M, Toko H, Koga K, Blanton RM Jr, Karas RH, Komuro I.
  • Journal Title: JACC Basic Transl Sci. Volume: 5 Pages: 282-295
  • DOI: 10.1016/j.jacbts.2019.12.009.
  • Peer Reviewed / Open Access
• [Journal Article] Comparison Between Healthcare-Associated and Community-Acquired Infective Endocarditis at Tertiary Care Hospitals in Japan. (2020)
  • Author(s): Kiriyama H, Daimon M, Nakanishi K, Kaneko H, Nakao T, Morimoto-Ichikawa R, Miyazaki S, Morita H, Daida H, Komuro I.
  • Journal Title: Circ J. Volume: 84 Pages: 670-676
  • DOI: 10.1253/circj.CJ-19-0887.
  • Peer Reviewed / Open Access
• [Journal Article] Association of short-term exposure to air pollution with myocardial infarction with and without obstructive coronary artery disease. (2020)
  • Author(s): Ishii M, Seki T, Kaikita K, Sakamoto K, Nakai M, Sumita Y, Nishimura K, Miyamoto Y, Noguchi T, Yasuda S, Kanaoka K, Terasaki S, Saito Y, Tsutsui H, Komuro I, Ogawa H, Tsujita K, Kawakami K; on the behalf of the JROAD Investigators.
  • Journal Title: Eur J Prev Cardiol. Volume: - Pages: -
  • DOI: 10.1177/2047487320904641.
  • Peer Reviewed / Open Access
• [Journal Article] Gender-specific association between the blood pressure category according to the updated ACC/AHA guidelines for hypertension and cardio-ankle vascular index: a community-based cohort study. (2020)
  • Author(s): Kamon T, Kaneko H, Itoh H, Kiriyama H, Mizuno Y, Morita H, Yamamichi N, Komuro I. Gender-specific association between the blood pressure category according to the updated ACC/AHA guidelines for hypertension and cardio-ankle vascular index: a community-based cohort study.
  • Journal Title: J Cardiol. Volume: 75 Pages: 578-582
  • DOI: 10.1016/j.jjcc.2019.10.007.
  • Peer Reviewed
• [Journal Article] Significant impact of left ventricular assist device models on the value of flow-mediated dilation: effects of LVAD on endothelial function. (2020)
  • Author(s): Watanabe A, Amiya E, Hatano M, Watanabe M, Ozeki A, Nitta D, Maki H, Hosoya Y, Tsuji M, Bujo C, Saito A, Endo M, Kagami Y, Nemoto M, Nawata K, Kinoshita O, Kimura M, Ono M, Komuro I.
  • Journal Title: Heart Vessels. Volume: 35 Pages: 207-213
  • DOI: 10.1007/s00380-019-01474-2.
  • Peer Reviewed
• [Journal Article] Controlling Nutritional Status Score As a Predictive Marker for Patients With Implantable Left Ventricular Assist Device. (2020)
  • Author(s): Saito A, Amiya E, Hatano M, Shiraishi Y, Nitta D, Minatsuki S, Maki H, Hosoya Y, Tsuji M, Bujo C, Nawata K, Kinoshita O, Kimura M, Endo M, Kagami Y, Nemoto M, Ikeda Y, Morita H, Ono M, Komuro I.
  • Journal Title: ASAIO J. Volume: 66 Pages: 166-172
  • DOI: 10.1097/MAT.0000000000000972.
  • Peer Reviewed
• [Journal Article] Quantification of DNA Damage in Heart Tissue as a Novel Prediction Tool for Therapeutic Prognosis of Patients With Dilated Cardiomyopathy. (2019)
  • Author(s): Ko T, Fujita K, Nomura S, Uemura Y, Yamada S, Tobita T, Katoh M, Satoh M, Ito M, Domoto Y, Hosoya Y, Amiya E, Hatano M, Morita H, Fukayama M, Aburatani H, Komuro I.
  • Journal Title: JACC Basic Transl Sci. Volume: 4 Pages: 670-680
  • DOI: 10.1016/j.jacbts.2019.05.010.
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of a small molecule that promotes cell cycle activation of human induced pluripotent stem cell-derived cardiomyocytes. (2019)
  • Author(s): Ito M, Hara H, Takeda N, Naito AT, Nomura S, Kondo M, Hata Y, Uchiyama M, Morita H, Komuro I.
  • Journal Title: J Mol Cell Cardiol. Volume: 128 Pages: 90-95
  • DOI: 10.1016/j.yjmcc.2019.01.020.
  • Peer Reviewed / Open Access
• [Journal Article] High-throughput single-molecule RNA imaging analysis reveals heterogeneous responses of cardiomyocytes to hemodynamic overload. (2019)
  • Author(s): Satoh M, Nomura S, Harada M, Yamaguchi T, Ko T, Sumida T, Toko H, Naito AT, Takeda N, Tobita T, Fujita T, Ito M, Fujita K, Ishizuka M, Kariya T, Akazawa H, Kobayashi Y, Morita H, Takimoto E, Aburatani H, Komuro I.
  • Journal Title: J Mol Cell Cardiol. Volume: 128 Pages: 77-89
  • DOI: 10.1016/j.yjmcc.2018.12.018.
  • Peer Reviewed / Open Access
• [Journal Article] Influence of visceral adiposity accumulation on adverse left and right ventricular mechanics in the community. (2019)
  • Author(s): Sawada N, Nakanishi K, Daimon M, Yoshida Y, Ishiwata J, Hirokawa M, Nakao T, Morita H, Di Tullio MR, Homma S, Komuro I.
  • Journal Title: Eur J Prev Cardiol. Volume: - Pages: -
  • DOI: 10.1177/2047487319891286.
  • Peer Reviewed / Open Access
• [Journal Article] Alteration of Cardiac Performance and Serum B-Type Natriuretic Peptide Level in Healthy Aging. (2019)
  • Author(s): Yoshida Y, Nakanishi K, Daimon M, Ishiwata J, Sawada N, Hirokawa M, Kaneko H, Nakao T, Mizuno Y, Morita H, Di Tullio MR, Homma S, Komuro I.
  • Journal Title: J Am Coll Cardiol. Volume: 74 Pages: 1789-1800
  • DOI: 10.1016/j.jacc.2019.07.080.
  • Peer Reviewed
• [Journal Article] Number of Cardiologists per Cardiovascular Beds and In-Hospital Mortality for Acute Heart Failure: A Nationwide Study in Japan. (2019)
  • Author(s): Kanaoka K, Okayama S, Nakai M, Sumita Y, Onoue K, Soeda T, Nishimura K, Kawakami R, Okura H, Miyamoto Y, Yasuda S, Tsutsui H, Komuro I, Ogawa H, Saito Y.
  • Journal Title: J Am Heart Assoc. Volume: 8 Pages: e012282
  • DOI: 10.1161/JAHA.119.012282.
  • Peer Reviewed / Open Access
• [Journal Article] Nationwide Actions Against Heart Failure Pandemic in Japan - What Should We Do From Academia? (2019)
  • Author(s): Komuro I, Kaneko H, Morita H, Isobe M, Nakayama H, Minematsu K, Yamaguchi T, Yazaki Y.
  • Journal Title: Circ J. Volume: 83 Pages: 1819-1821
  • DOI: 10.1253/circj.CJ-19-0562.
  • Peer Reviewed / Open Access
• [Journal Article] Overview of the 83rd Annual Scientific Meeting of the Japanese Circulation Society - Renaissance of Cardiology for the Creation of Future Medicine. (2019)
  • Author(s): Akazawa H, Toko H, Harada M, Ueda K, Kodera S, Kiyosue A, Fujiu K, Hatano M, Daimon M, Ando J, Takimoto E, Morita H, Komuro I.
  • Journal Title: Circ J. Volume: 83 Pages: 1829-1835
  • DOI: 10.1253/circj.CJ-19-0587.
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Treatment by Female Cardiologists on Short-Term Readmission Rates of Patients Hospitalized With Cardiovascular Diseases. (2019)
  • Author(s): Nakayama A, Morita H, Fujiwara T, Komuro I.
  • Journal Title: Circ J. Volume: 83 Pages: 1937-1943
  • DOI: 10.1253/circj.CJ-19-0357.
  • Peer Reviewed / Open Access
• [Journal Article] Impacts of Left Bundle/Peri-Left Bundle Pacing on Left Ventricular Contraction. (2019)
  • Author(s): Hasumi E, Fujiu K, Nakanishi K, Komuro I.
  • Journal Title: Circ J. Volume: 83 Pages: 1965-1967
  • DOI: 10.1253/circj.CJ-19-0399.
  • Peer Reviewed / Open Access
• [Journal Article] Macrophage hypoxia signaling regulates cardiac fibrosis via Oncostatin M. (2019)
  • Author(s): Abe H, Takeda N, Isagawa T, Semba H, Nishimura S, Morioka MS, Nakagama Y, Sato T, Soma K, Koyama K, Wake M, Katoh M, Asagiri M, Neugent ML, Kim JW, Stockmann C, Yonezawa T, Inuzuka R, Hirota Y, Maemura K, Yamashita T, Otsu K, Manabe I, Nagai R, Komuro I.
  • Journal Title: Nat Commun. Volume: 10 Pages: 2824
  • DOI: 10.1038/s41467-019-10859-w.
  • Peer Reviewed / Open Access
• [Journal Article] Clinical impact of newly developed atrial fibrillation complicated with longstanding ventricular fibrillation during left ventricular assist device support: A case report. (2019)
  • Author(s): Bujo C, Amiya E, Hatano M, Tsuji M, Maki H, Hosoya Y, Fujii E, Kamon T, Kojima T, Nawata K, Kinoshita O, Kimura M, Ono M, Komuro I.
  • Journal Title: BMC Cardiovasc Disord. Volume: 19 Pages: 151
  • DOI: 10.1186/s12872-019-1132-1.
  • Peer Reviewed / Open Access
• [Journal Article] Left Main Coronary Artery Obstruction by Huge Noncoronary Cusp Calcification After Transcatheter Aortic Valve Replacement. (2019)
  • Author(s): Kiriyama H, Kaneko H, Itoh H, Uehara M, Kodera S, Kiyosue A, Yamauchi H, Daimon M, Ando J, Morita H, Ono M, Komuro I.
  • Journal Title: JACC Cardiovasc Interv. Volume: 12 Pages: 1285-1287
  • DOI: 10.1016/j.jcin.2019.01.243.
  • Peer Reviewed
• [Journal Article] Relation between the Updated Blood Pressure Classification according to the American College of Cardiology/American Heart Association Guidelines and Carotid Intima-Media Thickness. (2019)
  • Author(s): Itoh H, Kaneko H, Kiriyama H, Yoshida Y, Nakanishi K, Mizuno Y, Daimon M, Morita H, Yatomi Y, Komuro I.
  • Journal Title: Am J Cardiol. Volume: 124 Pages: 396-401
  • DOI: 10.1016/j.amjcard.2019.04.054.
  • Peer Reviewed
• [Journal Article] Cost-Effectiveness of Percutaneous Coronary Intervention Compared With Medical Therapy for Ischemic Heart Disease in Japan. (2019)
  • Author(s): Kodera S, Morita H, Kiyosue A, Ando J, Komuro I.
  • Journal Title: Circ J. Volume: 83 Pages: 1498-1505
  • DOI: 10.1253/circj.CJ-19-0148.
  • Peer Reviewed / Open Access
• [Journal Article] The potential of cardiac rehabilitation as a method of suppressing abdominal aortic aneurysm expansion: a pilot study. (2019)
  • Author(s): Nakayama A, Amiya E, Morita H, Hyodo K, Takayama N, Konishi Y, Taya M, Fujiwara T, Hosoya Y, Hoshina K, Komuro I.
  • Journal Title: Heart Vessels. Volume: 34 Pages: 2031-2039
  • DOI: 10.1007/s00380-019-01441-x.
  • Peer Reviewed
• [Journal Article] Endothelial Cell-Derived Angiocrines Elicit Physiological Cardiomyocyte Hypertrophy. (2019)
  • Author(s): Ueda K, Toko H, Komuro I.
  • Journal Title: Circulation. Volume: 139 Pages: 2585-2587
  • DOI: 10.1161/CIRCULATIONAHA.119.040632.
  • Peer Reviewed
• [Journal Article] Genetic basis of hereditary thoracic aortic aneurysms and dissections. (2019)
  • Author(s): Takeda N, Komuro I.
  • Journal Title: J Cardiol. Volume: 74 Pages: 136-143
  • DOI: 10.1016/j.jjcc.2019.03.014.
  • Peer Reviewed
• [Journal Article] Progressive Right Ventricular Aneurysm in a Patient with Systemic Sarcoidosis. (2019)
  • Author(s): Hirose K, Amiya E, Ishizuka M, Uehara M, Komuro I.
  • Journal Title: J Cardiovasc Imaging. Volume: 27 Pages: 158-161
  • DOI: 10.4250/jcvi.2019.27.e18.
  • Peer Reviewed
• [Journal Article] Abdominal skeletal muscle mass as a predictor of mortality in Japanese patients undergoing left ventricular assist device implantation. (2019)
  • Author(s): Tsuji M, Amiya E, Hatano M, Nitta D, Maki H, Bujo C, Saito A, Hosoya Y, Minatsuki S, Hara T, Nemoto M, Kagami Y, Endo M, Kimura M, Kinoshita O, Nawata K, Morita H, Ono M, Komuro I.
  • Journal Title: ESC Heart Fail. Volume: 6 Pages: 526-535
  • DOI: 10.1002/ehf2.12429.
  • Peer Reviewed
• [Journal Article] Hospitalization Costs for Patients With Acute Congestive Heart Failure in Japan. (2019)
  • Author(s): Kanaoka K, Okayama S, Nakai M, Sumita Y, Nishimura K, Kawakami R, Okura H, Miyamoto Y, Yasuda S, Tsutsui H, Komuro I, Ogawa H, Saito Y.
  • Journal Title: Circ J. Volume: 83 Pages: 1025-1031
  • DOI: 10.1253/circj.CJ-18-1212.
  • Peer Reviewed / Open Access
• [Journal Article] The Significance of the Effect of Visceral Adiposity on Left Ventricular Diastolic Function in the General Population. (2019)
  • Author(s): Sawada N, Daimon M, Kawata T, Nakao T, Kimura K, Nakanishi K, Kurano M, Hirokawa M, Xu B, Yamanaka Y, Kato TS, Watanabe M, Yatomi Y, Komuro I.
  • Journal Title: Sci Rep. Volume: 9 Pages: 4435
  • DOI: 10.1038/s41598-018-37137-x.
  • Peer Reviewed / Open Access
• [Journal Article] Emergency percutaneous coronary intervention for left main trunk thrombus following orthotopic heart transplantation. (2019)
  • Author(s): Tsuji M, Nitta D, Minatsuki S, Maki H, Hosoya Y, Amiya E, Hatano M, Takimoto E, Kinoshita O, Nawata K, Ono M, Komuro I.
  • Journal Title: ESC Heart Fail. Volume: 6 Pages: 575-578
  • DOI: 10.1002/ehf2.12422.
  • Peer Reviewed
• [Journal Article] Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation. (2019)
  • Author(s): Yamada N, Asano Y, Komuro I, Yamagishi M, Horie M, Kawakami K, Furukawa T, Koizumi A, Kurachi Y, Sakata Y, Minamino T, Kitakaze M, Takashima S.
  • Journal Title: Circulation. Volume: 139 Pages: 2157-2169
  • DOI: 10.1161/CIRCULATIONAHA.118.036761.
  • Peer Reviewed
• [Presentation] Epigenetic Regulation of Cardiovascular Disease (2019)
  • Author(s): Issei Komuro
  • Organizer: Gordon Research Conference
  • Int'l Joint Research / Invited
• [Presentation] Molecular Mechanisms of Heart Failure Dissected by Single Cell RNA Saquence Analysis (2019)
  • Author(s): Issei Komuro
  • Organizer: 2019 XXIII ISHR WORLD CONGRESS
  • Int'l Joint Research / Invited
• [Presentation] Inflammageing (2019)
  • Author(s): Issei Komuro
  • Organizer: European Society of Cardiology
  • Int'l Joint Research / Invited
• [Presentation] 心不全パンデミック時代における研究の重要性 (2019)
  • Author(s): 小室一成
  • Organizer: 第29回日本心臓核医学会総会学術大会
  • Invited
• [Presentation] 日本腫瘍循環器学会の活動―個から組織へ (2019)
  • Author(s): 小室一成
  • Organizer: 第2回日本腫瘍循環器学会学術集会
  • Invited
• [Presentation] 基礎研究はどこまで循環器病の謎を解いたか -新しい循環器病学の時代へ (2019)
  • Author(s): 小室一成
  • Organizer: 第23回日本心不全学会
  • Invited
• [Presentation] 循環器学会の基本法への期待と学会会員諸氏への要望 (2019)
  • Author(s): 小室一成
  • Organizer: 第253回日本循環器学会関東甲信越地方会
  • Invited
• [Book] Cutting Edge of Molecular Cardiology 新しい臨床を開拓するための分子循環器病学 (2019)
  • Author(s): 小室一成
  • Total Pages: 210
  • Publisher: 南山堂
  • ISBN: 9784525249410
• [Book] 別冊医学のあゆみ 遺伝性心血管疾患のすべて (2019)
  • Author(s): 小室一成
  • Total Pages: 136
  • Publisher: 医歯薬出版
  • ISBN: 9784006028511
• [Patent(Industrial Property Rights)] 心不全患者の心機能回復可能性の評価方法 (2019)
  • Inventor(s): 野村征太郎、候聡志、油谷浩幸、小室一成
  • Industrial Property Rights Holder: 野村征太郎、候聡志、油谷浩幸、小室一成
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: PCT/JP2019/49960
  • Overseas
• [Patent(Industrial Property Rights)] 虚血性心疾患発症と予後を予測するゲノムリスクスコア (2019)
  • Inventor(s): 伊藤薫、野村征太郎、赤澤宏、小室一成
  • Industrial Property Rights Holder: 伊藤薫、野村征太郎、赤澤宏、小室一成
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 62935697