血管再構築・動脈硬化病変における造血幹細胞関与の分子機序と創薬標的の探索研究

2007 Fiscal Year Annual Research Report

• Project/Area Number: 18590986
• Research Institution: Kyoto University
• Principal Investigator: 横出 正之 Kyoto University, 医学研究科, 教授 (20252447)
• Co-Investigator(Kenkyū-buntansha): 荒井 秀典 京都大学, 医学研究科, 講師 (60232021) ; 村山 敏典 京都大学, 医学研究科, 助教 (30378765)
• Keywords: 動脈硬化 / 骨髄移植 / 造血幹細胞 / 高脂血症 / アポEノックアウトマウス

Research Abstract

平成19年度において申請者らは血管傷害反応としての血管再構築における骨髄由来幹細胞の関与を明らかにすることを引き続き目指した。申請者らは既にトロンボキサンA2受容体の骨髄由来の血球細胞での発現自体は粥状動脈硬化の進展制御に中枢的役割を果たさないことを実証したが、その一方で骨髄由来幹細胞の血管再構築過程において高脂血症が重要な制御メカニズムに関わることを新たに実証した。また申請者らは血管内皮細胞と粥状動脈硬化との関わりを探求する為、NF-kappaBならびにLox-1の発現制御メカニズムを追求し、その分子機構として桑葉に含有される抗酸化作用を有する水溶性分子が抗動脈硬化作用に関与することを証明した。以上の結果から、血管再構築と動脈硬化病変の発症、進展における高脂血症に代表される冠動脈リスクとの関わりにつき、酸化ストレス除去剤を含めた新たな動脈硬化症治療薬剤の創薬の可能性につき検索を続けている。

Research Products

• [Journal Article] Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy. (2007)
  • Author(s): Kanamori H, Matsubara T, Mima A, Sumi E, Nagai K, Takahashi T, Abe H, Iehara N, Fukatsu A, Okamoto H, Kita T, Doi T, Arai H.
  • Journal Title: Biochem Biophys Res Commun 360 Pages: 772-777
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Gender Difference In ICER Iγ Transgenic Diabetic Mouse. (2007)
  • Author(s): Inada A, Arai H, Nagai K, Miyazaki J, Nomura K, Kanamori H, Yamada Y, Akashi K, Weir GC, Seino Y, Fukatsu A
  • Journal Title: Bioscience, Biotechnology, and Biochemistry 71 Pages: 1920-1926
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Roles of coagulation pathway and factor Xa in rat mesangioproliferative glomerulonephritis. (2007)
  • Author(s): Nomura K, Liu N, Nagai K, Hasegawa T, Kobayashi I, Nogaki F, Tanaka M, Arai H, Fukatsu A, Kita T, Ono T
  • Journal Title: Lab Invent 87 Pages: 150-160
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Swimming reduces the severity of atherosclerosis in apolipoprotein E deficient mice by antioxidant effects. (2007)
  • Author(s): Okabe TA, Shimada K, Hattori M, Muravama T, Yokode M, Kita T, Kishimoto C.
  • Journal Title: Cardiovasc Res 74 Pages: 537-545
  • Peer Reviewed
• [Journal Article] Intramyocardial transplantation of autologous CD34+ stemcells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. (2007)
  • Author(s): Losordo DW, Schatz RA, White CJ, Udelson JE, Veereshwarayya V, Durgin M, Poh KK, Weinstein R, Kearney M, Chaudhry M, Burg A, Eaton L, Heyd L, Thorne T, Shturman L, Hoffmeister P, Story K, Zak V, Dowling D, Traverse JH, Olson RE, Flanagan J, Sodano D, Murayama T, Kawamoto A, Kusano KF, Wollins J, Welt F, Shah P, Soukas P, Asahara T, Henry TD.
  • Journal Title: Circulation 115 Pages: 3165-3172
  • Peer Reviewed
• [Journal Article] SRY-related HMG box 9 regulates the expression of Col4a2 through transactivating its enhancer element in mesangial cells. (2007)
  • Author(s): Sumi E, Iehara N, Akiyama H, Matsubara T, Mima A, Kanamori H, Fukatsu A, Salant DJ, Kita T, Arai H, Doi T.
  • Journal Title: Am J Pathol 170 Pages: 1854-1864
  • Peer Reviewed
• [Journal Article] Mulberry leaf powder prevents atherosclerosis in apolipoprotein E-deficient mice. (2007)
  • Author(s): Harauma A, Murayama T, Ikeyama K, Sano H, Arai H, Takano R, Kita T, Hara S, Kamei K, Yokode M.
  • Journal Title: Biochem Biophys Res Commun 358 Pages: 751-756
  • Peer Reviewed
• [Journal Article] Mulberry leaf aqueous fractions inhibit TNF-alpha-induced nuclear factor kappaB (NF-kappaB) activation and lectin-like oxidized LDL receptor-l (LOX-l) expression in vascular endothelial cells. (2007)
  • Author(s): Shibata Y, Kume N, Arai H, Hayashida K, Inui-Hayashida A, Minami M, Mukai E, Toyohara M, Harauma A, Murayama T, Kita T, Hara S, Kamei K, Yokode M.
  • Journal Title: Atherosclerosis 193 Pages: 751-756
  • Peer Reviewed
• [Journal Article] Hypercholesterolemia contributes to the development of atherosclerosis and vascular remodeling by recruiting bone marrow-derived cells in cuff-induced vascular injury. (2007)
  • Author(s): Xu Y, Arai H, Murayama T, Kita T, Yokode M.
  • Journal Title: Biochem Biophys Res Commun 363 Pages: 782-787
  • Peer Reviewed
• [Journal Article] Exercise training reduces severity of atherosclerosis in apolipoprotein E knockout mice via nitric oxide. (2007)
  • Author(s): Shimada K, Kishimoto C, Okabe TA, Hattori M, Murayama T, Yokode M, Kita T.
  • Journal Title: Circ J 71 Pages: 1147-1151
  • Peer Reviewed