Elucidation of the function of microRNAs on cardiovascular and metabolic disease : Investigation for a novel therapy by regulating microRNAs

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790703
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: HORIE Takahiro 京都大学, 医学研究科, 特定助教 (20565577)
• Project Period (FY): 2010 – 2011
• Keywords: マイクロRNA

Research Abstract

Small non-coding RNAs termed microRNAs, about 20bp, bind to the 3' UTR of target mRNAs and inhibit their expressions post-transcriptionally. Recently, dysregulation of microRNA expression or function has been found to be relevant to various diseases in human. In this study, we investigated the function of microRNAs on cardiovascular and metabolic diseases, and found that microRNA-33 regulated HDL cholesterol metabolism and microRNA-146a was associated with doxorubicin-induced cardiac damage.

Research Products

• [Journal Article] Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage (2011)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Kinoshita M, Watanabe S, Baba O, Kojima Y, Shizuta S, Imai M, Tamura T, Kita T, Kimura T
  • Journal Title: Circ Cardiovasc Genet Volume: 4 Pages: 446-454
  • DOI: DOI:10.1161/CIRCGENETICS.110.958975
  • Peer Reviewed
• [Journal Article] Distinct characteristics of circulating vascular endothelial growth factor-a and C levels in human subjects (2011)
  • Author(s): Wada H, Ura S, Kitaoka S, Satoh-Asahara N, Horie T, Ono K, Takaya T, Takanabe-Mori R, Akao M, Abe M, Morimoto T, Murayama T, Yokode M, Fujita M, Shimatsu A, Hasegawa K.
  • Journal Title: LoS One Volume: 6 Pages: 29351
  • DOI: DOI:10.1371/journal.pone.0029351
  • Peer Reviewed
• [Journal Article] コレステロールホメオスターシスとマイクロRNA (2011)
  • Author(s): 堀江貴裕、尾野亘、横出正之、木村剛
  • Journal Title: 血管医学 Volume: 12 Pages: 39-46
• [Journal Article] micro RNA-33は生体内でHDLコレステロールを制御する (2011)
  • Author(s): 尾野亘、堀江貴裕、木村剛、北徹
  • Journal Title: 実験医学 Volume: 29 Pages: 575-578
• [Journal Article] Micro RNA-33 encoded by an intron of Srebp2 regulates HDL in vivo (2010)
  • Author(s): Horie T, Ono K, Horiguchi M, Nishi H, Nakamura T, Nagao K, Kinoshita M, Kuwabara Y, Marusawa H, Iwanaga Y, Hasegawa K, Yokode M, Kimura T, Kita T
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 17321-6
  • Peer Reviewed
• [Journal Article] Regulation of adipocyte differentiation by activation of serotonin(5-HT) receptors 5-HT2AR and 5-HT2CR and involvement of microRNA-448-mediated repression of KLF5 (2010)
  • Author(s): Kinoshita M, Ono K, Horie T, Nagao K, Nishi H, Kuwabara Y, Takanabe-Mori R, Hasegawa K, Kita T, and Kimura T.
  • Journal Title: Molecular Endocrinology Volume: 24 Pages: 1978-87
  • Peer Reviewed
• [Journal Article] Acute Doxorubicin Cardiotoxicity Is Associated with miR-146a-induced Inhibition of the Neuregulin-ErbB Pathway (2010)
  • Author(s): Horie T, Ono K, Nishi H, Nagao K, Kinoshita M, Watanabe S, Kuwabara Y, Nakashima Y, Takanabe-Mori R, Nishi E, Hasegawa K, Kita T, Kimura T.
  • Journal Title: Cardiovascular Res Volume: 87 Pages: 656-664
  • Peer Reviewed
• [Journal Article] MicroRNA-15b modulates cellular ATP levels and degenerates mitochondria via ARL2 in neonatal rat cardiac myocytes (2010)
  • Author(s): Nishi H, Ono K, Iwanaga Y, Horie T, Nagao K, Takemura G, Kinoshita M, Kuwabara Y, Takanabe Mori R, Hasegawa K, Kita T, Kimura T.
  • Journal Title: J Biol Chem Volume: 285 Pages: 4920-30
  • Peer Reviewed
• [Journal Article] Neural cell adhesion molecule is a cardio protective factor up-regulated by metabolic stress (2010)
  • Author(s): Nagao K, Ono K, Iwanaga Y, Tamaki Y, Kojima Y, Horie T, Nishi H, Kinoshita M, Kuwabara Y, Hasegawa K, Kita T, Kimura T.
  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: 48 Pages: 1157-68
  • Peer Reviewed
• [Journal Article] LOX-1 is required for the adipose tissue expression of proinflammatory cytokines in high-fat diet-induced obese mice (2010)
  • Author(s): Takanabe-Mori R, Ono K, Sowa N, Takaya T, Horie T, Satoh-Asahara N, ShimatsuA, Fujita M, Sawamura T, Hasegawa K.
  • Journal Title: Biochem Biophys Res Commun Volume: 398 Pages: 576-80
  • Peer Reviewed
• [Presentation] MicroRNA-33 Regulates Atherosclerosis Formation (2012)
  • Author(s): Takahiro Horie, Osamu Baba, Koh Ono, Shin Watanabe, Hitoo Nishi, Minako Kinoshita, Yasuhide Kuwabara, Yoshimasa Chujo, Naoya Sowa, Koji Hasegawa, Noriaki Kum, Masayuki Yokode, Toru Kita, Takeshi Kimura
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡国際会議場(福岡)
  • Year and Date: 20120316-18
• [Presentation] Increased MicroRNA-1 and Micro RNA-133a Levels in Serum of Patients with Cardiovascular Disease Indicate the Existence of Myocardial Damage (2012)
  • Author(s): Koh Ono, Yasuhide Kuwabara, Takahiro Horie, Toru Kita, Takeshi Kimura
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 20120316-18
• [Presentation] Circulatin Micro RNAs Drived from Damaged Cardiomyocytes can Regulate the Gene Expression in Recipient CellsicroRNA-33 Regulates Atherosclerosis Formation (2012)
  • Author(s): Yasuhide Kuwabara, Koh Ono, Takahiro Horie, Hitoo Nishi, Shin Watanabe, Minako Kinoshita, Osamu Baba, Yoshimasa Chujo, Toru Kita, Takeshi Kimura
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 20120316-18
• [Presentation] MicroRNA 26b Encoded by the Intron of SCP1 Has an Antagonistic on its Host Gene and Cardiac Hypertrophy (2012)
  • Author(s): Naoya Sowa, Koh Ono, Takahiro Horie, Koji Hasegawa, Toru Kita, Takeshi Kimur
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 20120316-18
• [Presentation] Increased MicroRNA-1 and MicroRNA-133a Levels in Serum of Patients with Cardiovascular Disease Indicate the Existence of Myocardial Damage (2011)
  • Author(s): Yasuhide Kuwabara, Koh Ono, Takahiro Horie, Hitoo Nishi, Shin Watanabe, Minako Kinoshita, Osamu Baba, Yoshimasa Chujo, Kazuya Nagao, Yoji Kojima, Toru Kita, Takeshi Kimura
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orange County Convention Center(Orlando, USA)
  • Year and Date: 20111112-16
• [Presentation] MicroRNA 26b Encoded by the Intron of Small CTD Phosphatases(SCPs) Has an Antagonistic Effect on its Host Gene and Suppresses Cardiac Hypertrophy (2011)
  • Author(s): Naoya Sowa, Koh Ono, Takahiro Horie, Koji Hasegawa, Takeshi Kimura
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orange County Convention Center(Orlando, USA)
  • Year and Date: 20111112-16
• [Presentation] Elevated microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular diseases indicate the myocardial damage (2011)
  • Author(s): Y. Kuwabara, K. Ono, T. Horie, H. Nishi, S. Watanabe, M. Kinoshita, O. Baba, T. Kita, T. Kimura
  • Organizer: ESC Congress 2011
  • Place of Presentation: Paris Nord Villepinte(Paris, France)
  • Year and Date: 20110827-31
• [Presentation] CaMKK beta contributes to energy supply in adaptive phase of pressure-overload-induced heart failure (2011)
  • Author(s): S. Watanabe, K. Ono, T. Horie, H. Nishi, Y. Kuwabara, O. Baba, T. Kimura
  • Organizer: ESC Congress 2011
  • Place of Presentation: Paris Nord Villepinte(Paris, France)
  • Year and Date: 20110827-31
• [Presentation] MiR-146a-induced inhibition of the neuregulin-ErbB4 pathway may be involved in deterioration of cardiotoxicity under concurrent chemotherapy with doxorubicin and Trastuzumab (2010)
  • Author(s): Horie T, Ono K, Iwanaga Y, Nishi H, Nagao K, Kinoshita M, Watanabe S, Kuwabara Y, Nakashima Y, Takanabe-Mori R, Nishi E, Hasegawa K, Kita T, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions 2010
  • Place of Presentation: McCormick Place(Chicago, USA)
  • Year and Date: 20101113-17
• [Presentation] MicroRNA 26b family encoded by the introns of small CTD Phosphatases(SCPs) 1 to 3 suppresses phenylephrine-induced cardiomyocyte hypertrophy by targeting TRPC3/6 and GATA4 (2010)
  • Author(s): Ono K, Sowa N, Horie T, Hasegawa K, Kita T, Kimura T.
  • Organizer: American Heart Association Annual Scientific Sessions 2010
  • Place of Presentation: McCormickPlace(Chicago, USA)
  • Year and Date: 20101113-17
• [Presentation] Ca2+/Calumodulin-dependent kinase kinase beta contributes to energy supply in adaptive phase of pressure-overload-induced heart failure (2010)
  • Author(s): Watanabe S, Ono K, Horie T, Nishi H, Kinoshita M, Kuwabara Y, Baba O, Kimura T.
  • Organizer: American Heart Association Annual Scientific Sessions 2010
  • Place of Presentation: McCormick Place(Chicago, USA)
  • Year and Date: 20101113-17
• [Presentation] MicroRNA-27a regulates beta-myocin heavy chain gene expression by targeting thyroid hormone receptor beta 1 in neonatal rat ventricular myocytes (2010)
  • Author(s): Nishi H, Ono K, Horie T, Nagao K, Kinoshita M, Kuwabara Y, Baba O, Nakashima Y, Nagao K, Takanabe-Mori R, Hasegawa K, Kita T, Kimura T.
  • Organizer: American Heart Association Annual Scientific Sessions 2010
  • Place of Presentation: McCormick Place(Chicago, USA)
  • Year and Date: 20101113-17
• [Presentation] MicroRNA-1 and microRNA-133a are useful as early diagnostic biomarkers in patients with acute coronary syndrome (2010)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Kinoshita M, Watanabe S, Nakashima Y, Nagao K, Kojima Y, Kita T, Kimura T.
  • Organizer: American Heart Association Annual Scientific Sessions 2010
  • Place of Presentation: McCormick Place(Chicago, USA)
  • Year and Date: 20101113-17
• [Presentation] Ca2+/calmodulin-dependent kinase kinase beta contributes to energy supply in adaptive phase of pressure-overload-induced heart failure (2010)
  • Author(s): Watanabe S, Ono K, Horie T, Nishi H, Kuwabara Y, Kimura T.
  • Organizer: European Society of Cardiology Congress 2010
  • Place of Presentation: Stockholmsmassan(Stockholm, Sweden)
  • Year and Date: 20100828-0901
• [Presentation] MicroRNA-15b modulates cellular ATP levels and degenerates mitochondria via Arl2 in neonatal rat cardiac myocytes (2010)
  • Author(s): Ono K, Nishi H, Iwanaga Y, Horie T, Nagao K, Takemura G, Kinoshita M, Kuwabara Y, Takanabe-Mori R, Hasegawa K, Kita T, Kimura T.
  • Organizer: ISHR World Congress 2010 Kyoto
  • Place of Presentation: 京都国際会議場(京都)
  • Year and Date: 20100513-16
• [Presentation] ドキソルビシンによる心筋障害にはmiR-146aによるneuregulin/ErbBシグナルの抑制が関わる (2010)
  • Author(s): 堀江貴裕、尾野亘、西仁勇、長央和也、木下美菜子、桑原康秀、森利依子、長谷川浩二、北徹、木村剛
  • Organizer: 第47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(東京)
  • Year and Date: 20100410-11
• [Presentation] MicroRNA-448は脂肪細胞分化を抑制する (2010)
  • Author(s): 木下美菜子、尾野亘、桑原康秀、西仁勇、長央和也、堀江貴裕、森利依子、長谷川浩二、北徹、木村剛
  • Organizer: 第47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(東京)
  • Year and Date: 20100410-11
• [Presentation] SREBP2のイントロンにコードされるマイクロRNA-33は生体においてHDLの形成を制御する (2010)
  • Author(s): 堀江貴裕、尾野亘、西仁勇、長央和也、木下美菜子、桑原康秀、森利依子、長谷川浩二、北徹、木村剛
  • Organizer: 第2回京阪神心不全研究会
  • Place of Presentation: 阪急電鉄本社ビル1階(大阪)
  • Year and Date: 2010-12-04
• [Remarks]
  • URL: http://kyoto-u-cardio.jp/kisokenkyu/metabolic/