Analysis of Non-coding RNA Functions in Heart Diseases

• Project/Area Number: 26860556
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kyoto University
• Principal Investigator: Yasuhide Kuwabara 京都大学, 医学(系)研究科(研究院), 助教 (60632099)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 心不全 / 非コードRNA / 心肥大 / マイクロRNA

Outline of Final Research Achievements

Heart failure is a clinical syndrome, in which the heart can not pump the blood necessary in whole organs. In this investigation, we focused on the protein non-coding RNAs and tried to figure out the molecular mechanisms underlying cardiac hypertrophy and heart failure. It is known that type 2 diabetes and obesity induce cardiac hypertrophy and heart failure. During this research period, we found that miR-451, which is one of the non-coding RNAs, exacerbated the cardiac hypertrophy induced by obesity and type 2 diabetes by using cardiomyocyte-specific miR-451 knockout mice.
We also conducted the analysis of a long non-coding RNA, which is upregurated in heart failure, and got the interesting results.

Research Products

• [Int'l Joint Research] King's College London(United Kingdom)
• [Journal Article] MicroRNA-451 exacerbates lipotoxicity in cardiac myocytes and high-fat diet-induced cardiac hypertrophy in mice through suppression of the LKB1/AMPK pathway. (2015)
  • Author(s): Kuwabara Y, Horie T, Baba O, Watanabe S, Nishiga M, Usami S, Izuhara M, Nakao T, Nishino T, Otsu K, Kita T, Kimura T, Ono K.
  • Journal Title: Circulation Research Volume: 116 Issue: 2 Pages: 279-288
  • DOI: 10.1161/circresaha.116.304707
  • Peer Reviewed
• [Journal Article] Expression Patterns of miRNA-423-5p in the Serum and Pericardial Fluid in Patients Undergoing Cardiac Surgery. (2015)
  • Author(s): Miyamoto S, Usami S, Kuwabara Y, Horie T, Baba O, Hakuno D, Nakashima Y, Nishiga M, Izuhara M, Nakao T, Nishino T, Ide Y, Nakazeki F, Wang J, Ueyama K, Kimura T, Ono K.
  • Journal Title: PLoS One. Volume: 10(11) Issue: 11 Pages: e0142904-e0142904
  • DOI: 10.1371/journal.pone.0142904
  • NAID: 120005749912
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNAs and High-Density Lipoprotein Cholesterol Metabolism (2015)
  • Author(s): Ono K, Horie T, Nishino T, Baba O, Kuwabara Y, Kimura T.
  • Journal Title: International Heart Journal Volume: 56 Issue: 4 Pages: 365-371
  • DOI: 10.1536/ihj.15-019
  • NAID: 130005087574
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed / Open Access
• [Journal Article] High-density lipoprotein cholesterol levels and cardiovascular outcomes in Japanese patients after percutaneous coronary intervention: a report from the CREDO-Kyoto registry cohort-2. (2015)
  • Author(s): Izuhara M, Ono K, Shiomi H, Morimoto T, Furukawa Y, Nakagawa Y, Shizuta S, Tada T, Tazaki J, Horie T, Kuwabara Y, Baba O, Nishino T, Kita T, Kimura T; CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators.
  • Journal Title: Atherosclerosis. Volume: 242(2) Issue: 2 Pages: 632-8
  • DOI: 10.1016/j.atherosclerosis.2015.05.010
  • NAID: 120005678183
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-33a/b in Lipid Metabolism (2015)
  • Author(s): Ono K, Horie T, Nishino T, Baba O, Kuwabara Y, Yokode M, Kita T, Kimura T.
  • Journal Title: Circulation Journal Volume: 79 Issue: 2 Pages: 278-284
  • DOI: 10.1253/circj.CJ-14-1252
  • NAID: 130004927073
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1) exhibit reduced HDL-C in vivo. (2014)
  • Author(s): Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Nakazeki F, Ide Y, Koyama S, Sowa N, Yahagi N, Shimano H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 5312-5312
  • DOI: 10.1038/srep05312
  • Peer Reviewed / Open Access
• [Journal Article] Cardiac-Specific Inhibition of Kinase Activity in Calcium/Calmodulin-Dependent Protein Kinase Kinase-β Leads to Accelerated Left Ventricular Remodeling and Heart Failure after Transverse Aortic Constriction in Mice (2014)
  • Author(s): Shin Watanabe, Takahiro Horie, Kazuya Nagao, Yasuhide Kuwabara, Osamu Baba, Hitoo Nishi, Naoya Sowa, Michiko Narazaki, Tetsuya Matsuda, Genzou Takemura, Hiromichi Wada, Koji Hasegawa, Takeshi Kimura, Koh Ono
  • Journal Title: PLoS ONE Volume: 9 Issue: 9 Pages: e108201-e108201
  • DOI: 10.1371/journal.pone.0108201
  • NAID: 120005496630
  • Peer Reviewed / Open Access
• [Presentation] LincRNAs Regulated by Pressure-overload Induce Hypertrophy in Neonatal Mouse Cardiac Myocytes. (2016)
  • Author(s): Kuwabara Y, Horie T, Baba O, Nishiga M, Usami S, Izuhara M, Nakao T, Nishino T, Ide Y, Nakazeki F, Koyama S, Kita T, Kimura T, Ono K.
  • Organizer: The 80th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2016-03-18
  • Int'l Joint Research
• [Presentation] Long Intergenic Noncoding RNA and Myogenin Circuitry Promotes Myoblast Differentiation. (2016)
  • Author(s): Yasuhide Kuwabara, Takahiro Horie, Shin Watanabe, Osamu Baba, Takeshi Kimura, Koh Ono.
  • Organizer: Keystone Symposia, Noncoding RNAs in Health and Disease
  • Place of Presentation: Santa Fe, New Mexico, USA
  • Year and Date: 2016-02-21
  • Int'l Joint Research
• [Presentation] 虚血性心疾患の新規バイオマーカーとして、非コードRNAの可能性を探る (2015)
  • Author(s): 桑原康秀
  • Organizer: 第１回 Cardiac Biomarker研究会
  • Place of Presentation: 神戸シェラトン&タワーズ 神戸 兵庫
  • Year and Date: 2015-11-21
  • Invited
• [Presentation] マウス大動脈縮窄モデルにより増加するlincRNAはマウス心筋細胞において心肥大を誘導する (2015)
  • Author(s): 桑原康秀、堀江貴裕、馬場理、出原正康、宇佐美俊輔、西賀雅隆、西野共達、北徹、木村剛、尾野亘
  • Organizer: 第19回 日本心不全学術集会 ワーックショップ(6)
  • Place of Presentation: グランフロント大阪 ナレッジキャピタル コングレコンベンションセンター 大阪
  • Year and Date: 2015-10-22
• [Presentation] MicroRNA-451 Aggravates Lipotoxic Cardiomyopathy through Suppression of the LKB1/AMP Pathway. (2015)
  • Author(s): Yasuhide Kuwabara, Takahiro Horie, Osamu Baba, Toru Kita, Takeshi Kimura, Koh Ono.
  • Organizer: Basic Cardiovascular Sciences 2015
  • Place of Presentation: New Orleans, Louisiana, USA
  • Year and Date: 2015-07-13
  • Int'l Joint Research
• [Presentation] 肥大刺激によって誘導されるlincRNAの心臓と骨格筋における機能解析 (2015)
  • Author(s): 桑原康秀、堀江貴裕、馬場理、出原正康、宇佐美俊輔、中尾哲史、西賀雅隆、西野共達、井手裕也、中関典子、小山智史、木村剛、尾野亘
  • Organizer: 平成27年度 新学術領域班会議 生命素子による転写環境とエネルギー代謝のクロストーク制御「転写代謝システム」
  • Place of Presentation: 菊南温泉ユウベルホテル 熊本市 熊本
  • Year and Date: 2015-06-14
• [Presentation] MicroRNA-451 Induced by Palmitate Aggravates Diabetic Cardiomyopathy via Suppression of the LKB1/AMPK Signaling Pathway. (2015)
  • Author(s): Yasuhide Kuwabara, Takahiro Horie, Osamu Baba, Masayasu Izuhara, Shunsuke Usami, Tetsushi Nakao, Masataka Nishiga, Tomohiro Nishino, Yuya Ide, Fumiko Nakazeki, Satoshi Koyama, Koji Hasegawa, Toru Kita, Takeshi Kimura, Koh Ono.
  • Organizer: 20th Asian Pacific Society of Cardiology Congress
  • Place of Presentation: Abu Dhabi, UAE
  • Year and Date: 2015-04-29
  • Int'l Joint Research
• [Presentation] MicroRNA-451 is Involved in Diabetic Cardiomyopathy through LKB1/AMPK Pathway. (2015)
  • Author(s): Kuwabara Y, Horie T, Baba O, Nishiga M, Usami S, Izuhara M, Nakao T, Nishino T, Yuya Ide, Fumiko Nakazeki, Kimura T, Ono K.
  • Organizer: The 79th Annual Scientific Meeting of the Japanese Circulation Society,
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2015-04-24
  • Int'l Joint Research
• [Presentation] microRNA-451はLKB1-AMPK経路を抑制することで、ラット心筋細胞において細胞障害を、生体においては高脂肪食誘導性心肥大を誘導する (2015)
  • Author(s): 桑原康秀、堀江貴裕、馬場理、出原正康、宇佐美俊輔、中尾哲史、西賀雅隆、西野共達、北徹、木村剛、尾野亘
  • Organizer: 第52回 日本臨床分子医学会学術集会
  • Place of Presentation: みやこめっせ 京都
  • Year and Date: 2015-04-10
• [Presentation] 心肥大・心不全におけるlincRNAの機能解析 (2015)
  • Author(s): 桑原康秀、堀江貴裕、中島康弘、伯野大彦、馬場理、出原正康、宇佐美俊輔、西賀雅隆、西野共達、中尾哲史、井手裕也、中関典子、小山智史、北徹、木村剛、尾野亘
  • Organizer: 新学術領域研究 転写研究会＆転写サイクル＆転写代謝システム共催 若手ワークショップ
  • Place of Presentation: ホテル松本楼、渋川市伊香保町、群馬
  • Year and Date: 2015-02-05 – 2015-02-07
• [Presentation] MicroRNA-451 Exacerbates Lipotoxicity in Cardiomyocytes and High-Fat Diet-Induced Cardiac Hypertrophy in Mice through Suppression of the LKB1/AMPK Pathway. (2015)
  • Author(s): Yasuhide Kuwabara, Takahiro Horie, Osamu Baba, Shin Watanabe, Toru Kita, Takeshi Kimura, Koh Ono.
  • Organizer: Keystone Symposia, Mitochondria, Metabolism and Heart Failure joint with Diabetes and Metabolic Dysfunction.
  • Place of Presentation: Santa Fe, New Mexico, USA
  • Year and Date: 2015-01-27 – 2015-02-01
• [Presentation] 肥満を伴う糖尿病性心筋症における、microRNA-451の機能解析 (2014)
  • Author(s): 桑原康秀、堀江貴裕、馬場理、木村剛、尾野亘
  • Organizer: 第九回 高血圧と冠動脈疾患研究会
  • Place of Presentation: 大手町サンケイプラザ
  • Year and Date: 2014-12-20
• [Presentation] 飽和脂肪酸により誘導されるmicroRNA-451は、糖尿病性心筋症の増悪因子である。 (2014)
  • Author(s): 桑原康秀、堀江貴裕、馬場理、出原正康、宇佐美俊輔、中尾哲史、西賀雅隆、西野共達、井手裕也、中関典子、小山智史、木村剛、尾野亘
  • Organizer: 第37回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] MicroRNA-451 is Involved in Diabetic Cardiomyopathy through Suppression of the LKB1/AMPK Pathway. (2014)
  • Author(s): Yasuhide Kuwabara, Takahiro Horie, Osamu Baba, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Tetsushi Nakao, Tomohiro Nishino, Toru Kita, Takeshi Kimura, Koh Ono.
  • Organizer: 9th Metabolic Syndrome, Type 2 Diabetes and Atherosclerosis Congress.
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2014-09-12 – 2014-09-14
• [Presentation] 飽和脂肪酸により誘導されるmicroRNA-451は、糖尿病性心筋症の増悪因子である。 (2014)
  • Author(s): 桑原康秀、堀江貴裕、馬場理、出原正康、宇佐美俊輔、中尾哲史、西賀雅隆、西野共達、井手裕也、中関典子、小山智史、木村剛、尾野亘
  • Organizer: 第５回 Molecular Cardiovascular Conference II
  • Place of Presentation: 神戸ベイシェラトンホテル＆タワーズ
  • Year and Date: 2014-09-05 – 2014-09-06
• [Presentation] microRNA-451はLKB1-AMPK経路を抑制することで、ラット心筋細胞において細胞障害を、生体においては高脂肪食誘導性心肥大を誘導する。 (2014)
  • Author(s): 桑原康秀、堀江貴裕、馬場理、渡邉真、西賀雅隆、宇佐美俊輔、出原正康、中尾哲史、西野共達、木村剛、尾野亘
  • Organizer: 第51回 日本臨床分子医学会学術集会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2014-04-11 – 2014-04-12
• [Remarks] 京都大学医学部附属病院 循環器内科 心血管疾患分子機構解明グループ
  • URL: http://kyoto-u-cardio.jp/kisokenkyu/metabolic/
• [Remarks] 京都大学医学部附属病院 心血管疾患分子機構解明グループ
  • URL: http://kyoto-u-cardio.jp/kisokenkyu/metabolic/