Establishment of a novel therapeutic strategyfor atherosclerosis via soluble lipid transporter.

• Project/Area Number: 22590832
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Fukuoka University
• Principal Investigator: UEHARA Yoshinari 福岡大学, 医学部, 講師 (70373149)
• Co-Investigator(Kenkyū-buntansha): SAKU Keijiro 福岡大学, 医学部, 教授 (40183371) ; MATSUNAGA Youichi 徳島文理大学, 薬学部, 教授 (80239053)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 分子血管病態学 / 脂質 / 臨床 / リポ蛋白 / コレステロール / 膜輸送体 / 動脈硬化 / 低比重リポ蛋白 / 虚血性心臓病

Research Abstract

Our previous report shows the microglial ATP-binding cassette transporter(ABC) G4 has been upregulated in Alzheimer's disease (AD) brain. We had reported the cloning of a novel isoform of human ABCG4 which was short-isoform (SI) of ABCG4. SI-ABCG4 transfected cells expressed SI-ABCG4 proteins with both soluble and membrane bound forms. The SI-ABCG4 is possible to suppress HDL-mediated cholesterol efflux to interact with other lipid transporters such as ABCG1, ABCG4, and ABCA1. SI-ABCG4 could be a therapeutic tool and a novel marker foratherosclerosis related diseases.

Research Products

• [Journal Article] FAMP, A Novel ApoA-I Mimetic Peptide, Suppresses Aortic Plaque Formation Through Promotion of Biological HDL Function in ApoE-Deficient Mice (2013)
  • Author(s): Y Uehara, S Ando, E Yahiro, K Oniki, M Ayaori, S Abe, E Kawachi, B Zhang, S Shioi, H Tanigawa, S Imaizumi, S Miura, K Saku
  • Journal Title: J Am Heart Assoc. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Novel Molecular Imaging of Atherosclerosis with 68Ga-Labeled Apo A-I Mimetic Peptide and PET (2013)
  • Author(s): Kawachi E; Uehara Y; Hasegawa K; Yahiro E; Ando S; Wada Y; Yano T; Nishikawa H; Shiomi M; Miura S; Watanabe Y; Saku K
  • Journal Title: Circ J Volume: (in press)
  • Peer Reviewed
• [Journal Article] Possibility of increasing cholesterol efflux by adiponectin and its receptors through the ATP binding cassette transporter A1 in HEK293T cells (2011)
  • Author(s): Kitajima K, Miura SI, Yamauchi T, Uehara Y, Kiya Y, Rye KA, Kadowaki T, Saku K
  • Journal Title: Biochem Biophys Res Commun Volume: 411 Pages: 305-311
  • Peer Reviewed
• [Journal Article] Antiatherogenic effects of newly developed apolipoprotein A-I mimetic peptide/phospholipid complexes against aortic plaque burden in Watanabe-heritable hyperlipidemic rabbits. (2011)
  • Author(s): Iwata A, Miura SI, Zhang B, Imaizumi S, UeharaY, Shiomi M, Saku K.
  • Journal Title: Atherosclerosis Volume: 218 Pages: 300-307
  • Peer Reviewed
• [Journal Article] Effect of chronic kidney disease on excessive daytime sleepiness in Parkinson disease (2011)
  • Author(s): Baba Y, Higuchi MA, Fukuyama K, Abe H, Uehara Y
  • Journal Title: Eur J Neurol Volume: 18 Pages: 1299-1303
  • Peer Reviewed
• [Journal Article] Pioglitazone enhances cholesterol efflux from macrophages by increasing ABCA1/ ABCG1 expressions via PPARγ/LXRα pathway: Findings from in vitro and ex vivo studies (2011)
  • Author(s): OzasaH, AyaoriM, IizukaM, TeraoY, Uto-KondoH, YakushijiE, TakiguchiS, NakayaK,HisadaT, Uehara Y
  • Journal Title: Atherosclerosis Volume: 219 Pages: 141-150
  • Peer Reviewed
• [Journal Article] Tangier Disease (2011)
  • Author(s): Y.Uehara, B.Zhang, K.Saku
  • Journal Title: Advances in the Study of Genetic Disorders Volume: 8 Pages: 239-254
  • Peer Reviewed
• [Journal Article] Pioglitazone enhances cholesterol efflux from macrophages by increasing ABCA1/ABCG1 expressions via PPARγ/LXRα pathway : Findings from in vitro and ex vivo studies (2011)
  • Author(s): OzasaH, AyaoriM, IizukaM, TeraoY, Uto-KondoH, Yakushiji E, TakiguchiS, NakayaK, HisadaT, Uehara Y, et al
  • Journal Title: Atherosclerosis Volume: 219 Pages: 141-150
  • Peer Reviewed
• [Journal Article] Antiatherogenic effects of newly developed apolipoprotein A-I mimetic peptide/phospholipid complexes against aortic plaque burden in Watanabe-heritable hyperlipidemic rabbits (2011)
  • Author(s): Iwata A, Miura SI, Zhang B, Imaizumi S, Uehara Y, Shiomi M, Saku K
  • Journal Title: Atherosclerosis Volume: 218 Pages: 300-307
  • Peer Reviewed
• [Journal Article] A Randomized, Double-blind, Controlled, Comparative Trial of Formula Food Containing Soy Protein Versus Milk Protein in Visceral Fat Obesity : FLAVO study (2011)
  • Author(s): M-Takahira, K-Noda, M-Fukushima, B-Zhang, R-Mitsutake, Y-Uehara, M-Ogawa, T-Kakuma, K-Saku
  • Journal Title: Circ J Volume: 75 Pages: 2235-2243
  • Peer Reviewed
• [Journal Article] THE HDL HANDBOOK ; -Biological Functions and Clinical Implications ; -Chapter 7 : Apolipoprotein A-I Mutations/ (2010)
  • Author(s): Akira Matsunaga, Yoshinari Uehara, Bo Zhang, Keijiro Saku
  • Journal Title: Academic Press (ELSEVIER) Pages: 133-151
  • Peer Reviewed
• [Journal Article] A Randomized, Double-blind, Controlled, Comparative Trial of Formula Food Containing Soy Protein Versus Milk Protein in Visceral Fat Obesity: FLAVO study
  • Author(s): M-Takahira, K-Noda, M-Fukushima, B-Zhang, R-Mitsutake, Y-Uehara, M-Ogawa, T-Kakuma, K-Saku
  • Journal Title: Circ J 2011 Volume: 75 Pages: 2235-2243
  • Peer Reviewed
• [Presentation] A Small Peptide of ApoA-I Mimetic Works Anti-Atherosclerotic Effects by the Strength of HDL Function (2012)
  • Author(s): Y Uehara, K Oniki, T Shimizu, H Tanigawa, S Abe, S Ando, E Yahiro, S Imaizumi, S Miura, K Saku
  • Organizer: The 16th International Simposium on Atherosclerosis
  • Place of Presentation: Sydney
  • Year and Date: 2012-03-26
• [Presentation] A Small Peptide of ApoA-I Mimetic Works Anti-Atherosclerotic Effects by the Strength of HDL Function (2012)
  • Author(s): Y Uehara, K Oniki, T Shimizu, H Tanigawa, S Abe,S Ando, E Yahiro, S Imaizumi, S Miura, K Saku
  • Organizer: The 16th ISA meeting
  • Place of Presentation: Sydney, Australia
• [Presentation] A Novel ApoA-I mimetics, FAMP Constructs Pre-Beta HDL in vitro and in vivo (2011)
  • Author(s): Y.Uehara, K.Oniki, H.Tanigawa, S.Abe, S.Ando, E.Yahiro, SI.Miura, K.Saku
  • Organizer: The 79th European Atherosclerosis Society Congress
  • Place of Presentation: Gothenburg
  • Year and Date: 2011-06-28
• [Presentation] A Novel ApoA-I mimetics, FAMP Constructs Pre-Beta HDL in vitro and in vivo (2011)
  • Author(s): Y. Uehara, K. Oniki, H. Tanigawa, S. Abe, S. Ando, E. Yahiro, SI. Miura, K. Saku
  • Organizer: The79th European Atherosclerosis Society Congress.
  • Place of Presentation: Gothenburg, Sweden
• [Presentation] FAMP, A Promising Anti-atherosclerotic Agent Construct Pre-Beta HDL in vitro and in vivo (2011)
  • Author(s): Y. Uehara, K. Oniki, H. Tanigawa, S. Abe, S. Ando, E. Yahiro, SI. Miura, K. Saku
  • Organizer: 第43回日本動脈硬化学会総会
  • Place of Presentation: 札幌
• [Presentation] 新規可溶型トランスポーター(ABCG4)の同定とアルツハイマー病との関連性 (2011)
  • Author(s): 上原吉就,阿部智美,馬場康彦,朔啓二郎,山田達夫
  • Organizer: 第21回日本老年医学会九州地方会
  • Place of Presentation: 福岡
• [Presentation] IDENTIFICATION AND CLONING OF NOVEL SOLUBLE AND MEMBRANE BOUND FORMS OF HUMAN ATP-BINDING CASSETTE TRANSPORTER G4 (2010)
  • Author(s): Y.Uehara, S.Abe, E.Yahiro, A.Kawamura, T.Iwamoto, SI.Miura, K.Saku
  • Organizer: 78^<th> European Atherosclerosis Society Meeting
  • Place of Presentation: Hamburg(ドイツ)
  • Year and Date: 2010-06-22
• [Presentation] IDENTIFICATION AND CLONING OF NOVEL SOLUBLE AND MEMBRANE BOUND FORMS OF HUMAN ATP-BINDING CASSETTE TRANSPORTER G4 (2010)
  • Author(s): Y.Uehara, S.Abe, E.Yahiro, A.Kawamura, T.Iwamoto, SI.Miura, K.Saku
  • Organizer: 78th EAS Meeting
  • Place of Presentation: Hamburg, Germany
• [Book] Advances in the Study of Genetic Disorders (2011)
  • Author(s): Y. Uehara, B. Zhang, K. Saku
  • Publisher: Tangier Disease
• [Book] Biological Functions and Clinical Implications; ApoA-I Mutations (2010)
  • Author(s): A.Matsunaga, Y.Uehara, B.Zhang, K.Saku
  • Publisher: Academic Press (ELSEVIER)