Investigation of the novel prevention and treatment for atherosclerosis by microRNA modulation

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790753
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: HORIE TAKAHIRO 京都大学, 医学(系)研究科(研究院), 助教 (20565577)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: マイクロRNA / 動脈硬化 / HDL

Research Abstract

Endogenous small RNAs, called microRNA, regulate gene expression precisely and it has been clear that microRNAs are involved in various kinds of disease formation. Previously, we showed that microRNA-33 (miR-33) which is located in the intron of SREBP2 regulates intracellular cholesterol homeostasis and HDL cholesterol formation. In this study, we explored the impact of miR-33 on atherosclerosis formation. miR-33 deficiency under apoE deficient mice background showed reduced atherosclerosis formation via upregulation of serum HDL levels and phenotypic changes of macrophages. These results indicated that miR-33 could become the new target of the arteriosclerosis treatment.

Research Products

• [Journal Article] MicroRNAs and lipoprotein metabolism (2014)
  • Author(s): Horie-T, Baba-O, Kuwabara-Y, Yokode-M, Kita-T, Kimura-T, Ono-K
  • Journal Title: J Atheroscler Thromb Volume: 21 Pages: 17-22
  • URL: https://www.jstage.jst.go.jp/articla/jat/21/1/21_20859/_article
  • Peer Reviewed
• [Journal Article] MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice (2013)
  • Author(s): Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Sowa N, Yahagi N, Shimano H, Matsumura S, Inoue K, Marusawa H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, and Ono K
  • Journal Title: Nat Commun Volume: 4 Pages: 2883
  • DOI: 10.1038/ncomms3883
  • Peer Reviewed
• [Journal Article] Metastasis-associated protein, S100A4 mediates cardiac fibrosis potentially through the modulation of p53 in cardiac fibroblasts (2013)
  • Author(s): Tamaki Y, Iwanaga Y, Niizuma S, Kawashima T, Kato T, Inuzuka Y, Horie T, Morooka H, Takase T, Akahashi Y, Kobuke K, Ono K, Shioi T, Sheikh SP, Ambartsumian N, Lukanidin E, Koshimizu TA, Miyazaki S, Kimura T
  • Journal Title: J Mol Cell Cardiol Volume: 57 Pages: 72-81
  • DOI: 10.1016/j.yjmcc.2013.01.007
  • Peer Reviewed
• [Journal Article] MicroRNA-33-deficiency reduces the progression of atherosclerotic plaque in apoE-/- mice (2012)
  • Author(s): Horie T, Baba O, Kuwabara Y, Chujo Y, Watanabe S, Kinoshita M, Horiguchi M, Nakamura T, Chonabayashi K, Hishizawa M, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K
  • Journal Title: J Am Heart Assoc Volume: 1 Pages: e003376
  • DOI: 10.1161/JAHA.112.003376.
  • Peer Reviewed
• [Journal Article] Roles of MicroRNAs and Myocardial Cell Differentiation (2012)
  • Author(s): Takaya T, Nishi H, Horie T, Ono K, Hasegawa K
  • Journal Title: Prog Mol Biol Transl Sci Volume: 111 Pages: 139-52
  • DOI: 10.1016/B978-0-12-398459-3.
  • Peer Reviewed
• [Journal Article] Micro RNA 26b Encoded by the Intron of Small CTD Phosphatase (SCP) 1 Has an Antagonistic Effect on its Host Gene (2012)
  • Author(s): Sowa N, Horie T, Kuwabara Y, Baba O, Watanabe S, Nishi H, Kinoshita M, Takanabe-Mori R, Wada H, Shimatsu A, Hasegawa K, Kimura T, and Ono K.
  • Journal Title: Journal of Cellular Biochem Volume: 113 Pages: 3455-65
  • DOI: 10.1002/jcb.24222.
  • Peer Reviewed
• [Presentation] MicroRNA-33 Encoded by an Intron of Sterol Regulatory Element-Binding Protein 2 (Srebp2) Regulates Srebp1 in vivo. Yasuhide Kuwabara,MicroRNA-451 Exacerbates Lipotoxicity in Neonatal Rat Cardiomyocytes, and High Fat Diet Induced Cardiac Hypertrophy in Mice through LKB1/AMPK Pathway. (2014)
  • Author(s): Takahiro Horie, Tomohiro Nishino, Osamu Baba, Yasuhide Kuwabara, Tetsushi Nakao, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Naoya Sowa, Naoya Yahagi, Hitoshi Shimano, Masayuki Yokode, Toru Kita, Takeshi Kimura, Koh Ono,Takahiro Horie, Osamu Baba, Shin Watanabe, Masayasu Izuhara, Tetsushi Nakao, Shunsuke Usami, Tomohiro Nishino, Masataka Nishiga, Toru Kita, Takeshi Kimura, Koh Ono
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 20140321-23
• [Presentation] SREBP-2のイントロンに存在するマイクロRNA-33はSREBP-1の発現を制御する,microRNA-451 はLKBA-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による心肥大を誘導する (2014)
  • Author(s): 堀江貴裕、西野共達、馬場理、桑原康秀、 中尾哲史、西賀雅隆、宇佐美俊輔、出原 正康、矢作直也、島野仁、横出正之、北 徹、木村剛、尾野亘,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、井出裕也、中関典子、木村剛、尾 野亘
  • Organizer: 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2014』
  • Place of Presentation: 群馬県 磯部温泉
  • Year and Date: 20140130-0201
• [Presentation] MicroRNA-33 Deficiency Reduces the Progression of Atherosclerotic Plaque in ApoE-/- Mice (2013)
  • Author(s): 堀江貴裕、馬場 理、木村 剛、尾野 亘
  • Organizer: 第45回日本動脈硬化学会
  • Place of Presentation: 京王プラザホテルイブニングセミナー2
  • Year and Date: 20130718-19
• [Presentation] MicroRNA-33 deficiency reduces atherosclerosis formation in vivo. (2013)
  • Author(s): 堀江貴裕
  • Organizer: 成人病の病因・病態の解明に関する研究助成第19回研究発表会(TMFC)
  • Place of Presentation: 大阪 セントレジスホテル大阪
  • Year and Date: 20130706-07
• [Presentation] マイクロRNA-33欠損はアポE欠損マウスにおいて動脈硬化形成を抑制する (2013)
  • Author(s): 堀江貴裕
  • Organizer: 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@鬼怒川』
  • Place of Presentation: 栃木ホテル鬼怒川御苑
  • Year and Date: 20130124-26
• [Presentation] マイクロRNA制御による新規動脈硬化治療法の探索的研究 (2013)
  • Author(s): 堀江貴裕、馬場理、桑原康秀、横出正之、北徹、木村剛、尾野亘
  • Organizer: 第八回高血圧と冠動脈疾患研究会
  • Place of Presentation: 大手町産経プラザ4階 『サンケイホール』
  • Year and Date: 2013-12-21
• [Presentation] MicroRNA encoded by an intron of Srebf2 regulates SREBP-1 in vivo. (2013)
  • Author(s): Takahiro Horie
  • Organizer: 平成25年度新学術領域「転写代謝システム」第5回総括班会議 国際シンポジウム
  • Place of Presentation: 淡路夢舞台国際 会議場
  • Year and Date: 2013-11-11
• [Presentation] マイクロRNA-33欠損はアポE欠損マウスにおいて動脈硬化形成を抑制する (2013)
  • Author(s): 堀江貴裕、馬場 理、桑原康秀、久米典 昭、横出正之、北徹、木村 剛、尾野 亘
  • Organizer: 第50回日本臨床分子医学会学術集会
  • Year and Date: 2013-04-12
• [Presentation] MicroRNA-33 deficiency reduces atherosclerosis formation in vivo. (2012)
  • Author(s): Takahiro Horie, Osamu Baba, Koh Ono, Yasuhide Kuwabara, Naoya Sowa, Koji Hasegawa, Noriaki Kume, Masayuki Yokode, Toru Kita, Takeshi Kimura
  • Organizer: 第20回日本血管生物医学会学術集会[併催] 第10回Korea-Japan Joint Symposium on Vascular Biology
  • Place of Presentation: 徳島あわぎんホール
  • Year and Date: 20121205-07
• [Presentation] MicroRNA-33 Deficiency Reduced Atherosclerosis Formation In Vivo.,MicroRNA 33 Deficiency in Leukocytes Reduced the Lipid Accumulation in Atherosclerotic Plaque in ApoE Knockout Mice. (2012)
  • Author(s): Horie T, Baba O, Ono K, Kuwabara Y, Hasegawa K, Kume N, Yokode M, Kita T, and Kimura T,Baba O, Horie T, Kuwabara Y, Izuhara M, Usami S, Nakao T, Nishiga M, Nishino T, Sowa N, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, and Ono K
  • Organizer: American Heart Association Annual Scientific Sessions 2012
  • Place of Presentation: Los Angeles Convention Center
  • Year and Date: 20121103-07
• [Presentation] MicroRNA-33 deficiency reduced atherosclerosis formation in vivo. (2012)
  • Author(s): Takahiro Horie, Osamu Baba, Koh Ono, Yasuhide Kuwabara, Naoya Sowa, Koji Hasegawa, Noriaki Kume, Masayuki Yokode, Toru Kita, Takeshi Kimura
  • Organizer: 第3回 Molecular Cardiovascular ConferenceII
  • Place of Presentation: 北海道キロロ
  • Year and Date: 20120907-09
• [Presentation] MicroRNA 33 Deficiency Reduces Atherosclerotic Plaque progression in ApoE Knockout Mice. (2012)
  • Author(s): Baba O, Horie T, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, and Ono K
  • Organizer: European Society of Cardiology Congress 2012
  • Place of Presentation: Germany
  • Year and Date: 20120825-29
• [Presentation] マイクロRNA-33欠損は動脈硬化形成を抑制する (2012)
  • Author(s): 堀江貴裕、馬場理、尾野亘、桑原康秀、 曽和尚也、長谷川浩二、久米典昭、横出正之、北徹、木村剛
  • Organizer: 平成24年度『転写代謝システム領域班会議
  • Place of Presentation: 筑波グランドホテル
  • Year and Date: 20120702-04
• [Presentation] マイクロRNA-33は動脈硬化形成を制御する (2012)
  • Author(s): 堀江貴裕、馬場理、尾野亘、渡邉真、西 仁勇、木下美菜子、桑原康秀、中條克真、横出正之、木村剛
  • Organizer: 第109回日本内科学会講演会
  • Place of Presentation: 京都みやこメッセ
  • Year and Date: 20120413-15
• [Presentation] マイクロRNA-33欠損は動脈硬化形成を抑制する (2012)
  • Author(s): 堀江貴裕
  • Organizer: 第49回日本臨床分子医学会学術集会
  • Place of Presentation: 京都みやこメッセ
  • Year and Date: 20120413-14
• [Presentation] 動脈硬化形成過程におけるマイクロRNAの機能解析～新規動脈硬化治療法の開発を目指して～ (2012)
  • Author(s): 堀江貴裕
  • Organizer: 第1回万有医学奨励賞報告会
  • Place of Presentation: 東京 品川ラフォーレ
  • Year and Date: 2012-12-08
• [Presentation] MicroRNA-33 Deficiency Reduced Atherosclerosis Formation In Vivo. (2012)
  • Author(s): Horie T, Baba O, Ono K, Kuwabara Y, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T
  • Organizer: ATVB Early Career Networking Reception
  • Place of Presentation: Westin Bonaventure Hotel & Suites, Los Angeles, CA
  • Year and Date: 2012-11-06
• [Presentation] MicroRNA-33 deficiency reduced atherosclerosis formation in vivo. (2012)
  • Author(s): Takahiro Horie, Osamu Baba, Koh Ono, Shin Watanabe, Hitoo Nishi, Minako Kinoshita, Yasuhide Kuwabara, Yoshimasa Chujo, Naoya Sowa, Koji Hasegawa, Noriaki Kume, Masayuki Yokode, Toru Kita, Takeshi Kimura
  • Organizer: 第44回日本動脈硬化学会学術集会
  • Place of Presentation: 博多
  • Year and Date: 2012-07-19
• [Presentation] MicroRNA-33 deficiency reduces atherosclerosis formation in vivo.
  • Author(s): Takahiro Horie, Osamu Baba, Masataka Nishiga, Koji Hasegawa, Masayuki Yokode, Takeshi Kimura, Koh Ono
  • Organizer: 18th Annual Scientific Meeting of the International Society of Cardiovascular Pharmacotherapy 28th-30th June
  • Place of Presentation: Italy, Roma
• [Book] マイクロRNA-33の動脈硬化形成における機能・役割について
  • Author(s): 堀江貴裕
  • Total Pages: 36-37
  • Publisher: Asahi Medical
• [Remarks]
  • URL: http://kyoto-u-cardio.jp/kisokenkyu/metabolic/