Cardiovascular-endocrinological approach for elucidation of the molecular mechanism of "Metabo-aging"

2008 Fiscal Year Final Research Report

• Project/Area Number: 19390255
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Keio University
• Principal Investigator: ITOH Hiroshi Keio University, 医学部, 教授 (40252457)
• Co-Investigator(Kenkyū-buntansha): WAKINO Shu 慶應義塾大学, 医学部, 講師 (50265823) ; TANIGAWARA Yusuke 慶應義塾大学, 医学部, 教授 (30179832) ; HOSODA Kiminori 京都大学, 医学研究科, 講師 (40271598) ; SONE Masakatsu 京都大学, 医学研究科, 助教 (40437207)
• Project Period (FY): 2007 – 2008
• Keywords: メタボリックシンドローム / エイジング / 心血管ホルモン / NO / cGMPナトリウム利尿ペプチド / アンジオテンシン / ミトコンドリア

Research Abstract

本研究ではメタボリックシンドロームとその合併症を、エネルギー代謝状態の変化に伴う加齢現象すなわちメタボエイジングとして捉え、代謝性疾患から循環器疾患に至る一連の疾患群の分子機構ならびに心血管ホルモンの意義に関して検討を続けた。本年度までに(1) 血管ホルモンによるミトコンドリア制御と代謝調節(2) ADMAによるNO産生阻害の循環器疾患発症における意義(3) 長寿制御因子Sirt1の腎疾患発症における意義(4) プロレニン受容体を介したシグナル伝達経路の循環器疾患発症における意義(5) アンジオテンシンIIレセプターブロッカーパルス療法による高血圧の退縮に関して新たな知見を得た。

Research Products

• [Journal Article] Drug discovery for overcoming chronic kidney disease (CKD) : new therapy for CKD by a (pro)renin-receptor-blocking decoy peptide. (2009)
  • Author(s): Ichihara A, Sakoda M, Kurauchi-Mito A, Narita T, Kinouchi K, Itoh H.
  • Journal Title: J Pharmacol Sci. 109(1) Pages: 20-23
• [Journal Article] "Pulse" treatment with high-dose angiotensin blocker reverses renal arteriolar hypertrophy and regresses hypertension (2009)
  • Author(s): Ishiguro K, Hayashi K, Sasamura H, Sakamaki Y, Itoh H.
  • Journal Title: Hypertension 53(1) Pages: 83-89
• [Journal Article] Angiotensin II Reduces Mitochondrial Content in Skeletal Muscle and Affects Glycemic Control (2009)
  • Author(s): Mitsuishi M, Miyashita K, Muraki A, Itoh H.
  • Journal Title: Diabetes(Epub 2008 Dec 15) 58(3) Pages: 710-717
• [Journal Article] Transplantation of vascular cells derived from human embryonic stem cells contributes to vascular regeneration after stroke in mice (2008)
  • Author(s): Oyamada N, Itoh H, Sone M, Yamahara K, Miyashita K, Kwijun P, Taura D, Inuzuka M, Sonoyama T, Tsujimoto H, Fukunaga Y, Tamura N, Nakao K.
  • Journal Title: J Transl Med(Epub ahead of print) 30 ; 6(1) Pages: 54
• [Journal Article] Differential effects of transient treatment of spontaneously hypertensive rats with various antihypertensive agents on the subsequent development of diabetic nephropathy (2008)
  • Author(s): Ishiguro K, Sasamura H, Sakamaki Y, Hayashi K, Saruta T, Itoh H
  • Journal Title: Nephron Exp Nephrol(Epub 2008 May 28) 109(1) Pages: 20-28
• [Journal Article] Sirt1 protects against oxidative stress-induced renal tubular cell apoptosis by the bidirectional regulation of catalase expression (2008)
  • Author(s): Hasegawa K, Wakino S, Yoshioka K, Tatematsu S, Hara Y, Minakuchi H, Washida N, Tokuyama H, Hayashi K, Itoh H.
  • Journal Title: Biochem Biophys Res Commun(Epub 2008 May 15) 18 ; 372(1) Pages: 51-56
• [Journal Article] The role of mineralocorticoid receptor expression in brain remodeling after cerebral ischemia (2008)
  • Author(s): Oyamada N, Sone M, Miyashita K, Park K, Taura D, Inuzuka M, Sonoyama T, TsujimotoH, Fukunaga Y, Tamura N, Itoh H, Nakao K.
  • Journal Title: Endocrinology(Epub 2008 Apr 24) 149(8) Pages: 3764-3777
• [Journal Article] Involvement of (pro) renin receptor in the glomerular filtration barrier (2008)
  • Author(s): Ichihara A, Sakoda M, Kurauchi-Mito A, Kaneshiro Y, Itoh H.
  • Journal Title: J Mol Med.(Epub 2008 Mar 12) 86(6) Pages: 629-635
• [Journal Article] Augmentation of neovascularizaiton in hindlimb ischemia by combined transplantation of human embryonic stem cells-derived endothelial and mural cells (2008)
  • Author(s): Yamahara K, Sone M, Itoh H, Yamashita JK, Yurugi-Kobayashi T, Homma K, Chao TH, Miyashita K, Park K, Oyamada N, Sawada N, Taura D, Fukunaga Y, Tamura N, Nakao K.
  • Journal Title: PLoS ONE 27 ; 3(2) Pages: 1666
• [Journal Article] cGMP rescues mitochondrial dysfunction induced by glucose and insulin in myocytes (2008)
  • Author(s): Mitsuishi M, Miyashita K, Itoh H.
  • Journal Title: Biochem Biophys Res Commun(Epub 2008 Jan 14) 367(4) Pages: 840-845
• [Journal Article] Greater impact of oral fluconazole on drug interaction with intravenous calcineurin inhibitors as compared with intravenous fluconazole (2008)
  • Author(s): Mihara A, Mori T, Aisa Y, Yamazaki R, Iketani O, Tanigawara Y, Ikeda Y, Okamoto S.
  • Journal Title: Eur J Clin Pharmacol 64 Pages: 89-91
• [Journal Article] Therapeutic potential of atrial natriuretic peptide administration on peripheral arterial diseases (2008)
  • Author(s): Park K, Itoh H, Yamahara K, Sone M, Miyashita K, Oyamada N, Sawada N, Taura D, Inuzuka M, Sonoyama T, Tsujimoto H, Fukunaga Y, Tamura N, Nakao K.
  • Journal Title: Endocrinology(Epub 2007 Nov 8) 149(2) Pages: 483-491
• [Journal Article] Pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration (2007)
  • Author(s): Sone M, Itoh H, Yamahara K, Yamashita JK, Yurugi-Kobayashi T, Nonoguchi A, Suzuki Y, Chao TH, Sawada N, Fukunaga Y, Miyashita K,Park K,Oyamada N,Sawada N,Taura D,Tamura N, Kondo Y, Nito S, Suemori H, Nakatsuji N, Nishikawa S, Nakao K.
  • Journal Title: Arterioscler Thromb Vasc Biol(Epub 2007 Sep 13) 27(10) Pages: 2127-2134
• [Journal Article] (Pro)renin receptor-mediated activation of mitogen-activated protein kinases in human vascular smooth muscle cells (2007)
  • Author(s): Sakoda M, Ichihara A, Kaneshiro Y, Takemitsu T, Nakazato Y, Nabi AH, Nakagawa T, Suzuki F, Inagami T, Itoh H.
  • Journal Title: Hypertens Res. 30(11) Pages: 1139-1146
• [Journal Article] Snail1 is involved in the renal epithelial-mesenchymal transition (2007)
  • Author(s): Yoshino J, Monkawa T, Tsuji M, Inukai M, Itoh H, Hayashi M.
  • Journal Title: Biochem Biophys Res Commun(Epub 2007 Aug 3) 362(1) Pages: 63-68
• [Journal Article] Genetic and pharmacological inhibition of Rho-associated kinase II enhances adipogenesis (2007)
  • Author(s): Noguchi M, Hosoda K, Fujikura J, Fujimoto M, Iwakura H, Tomita T, Ishii T, Arai N, Hirata M, Ebihara K, Masuzaki H, Itoh H, Narumiya S, Nakao K.
  • Journal Title: J Biol Chem(Epub 2007 Aug 6) 282(40) Pages: 29574-29583
• [Journal Article] Role of asymmetric dimethylarginine in vascular injury in transgenic mice overexpressing dimethylarginie dimethylaminohydrolase 2 (2007)
  • Author(s): Hasegawa K, Wakino S, Tatematsu S, Yoshioka K, Homma K, Sugano N, Kimoto M, Hayashi K, Itoh H.
  • Journal Title: Circ Res.(Epub 2007 Jun 29) 101(2) Pages: 2-10
• [Journal Article] Regression of nephropathy developed in diabetes by (Pro) renin receptor blockade (2007)
  • Author(s): Takahashi H, Ichihara A, Kaneshiro Y, Inomata K, Sakoda M, Takemitsu T, Nishiyama A, Itoh H.
  • Journal Title: J Am Soc Nephrol(Epub 2007 May 30) 18(7) Pages: 2054-2061
• [Journal Article] Slowly progressive, angiotensin II-independent glomerulosclerosis in human (pro) renin receptor-transgenic rats (2007)
  • Author(s): Kaneshiro Y, Ichihara A, Sakoda M, Takemitsu T, Nabi AH, Uddin MN, Nakagawa T, Nishiyama A, Suzuki F, Inagami T, Itoh H.
  • Journal Title: J Am Soc Nephrol(Epub 2007 May 9) 18(6) Pages: 1789-1795
• [Journal Article] Phase II Study of Oxaliplatin in Japanese Patients with Metastatic Colorectal Cancer Refractory to Fluoropyrimidines (2007)
  • Author(s): Boku N, Ohtsu A, Hyodo I, Shirao K, Miyata Y, Nakagawa K, Tamura T, Hatake K, Tanigawara Y.
  • Journal Title: Jpn J Clin Oncol 37 Pages: 440-445
• [Patent(Industrial Property Rights)] 抗がん剤感受性判定マーカー (2008)
  • Inventor(s): 谷川原祐介・渡辺光博・有田惠理・西牟田章戸・山吉康子・松崎健・杉本伸二
  • Industrial Property Rights Holder: 学校法人慶應義塾、株式会社ヤクルト
  • Industrial Property Number: 特許, 特願2008-021123号
  • Filing Date: 2008-01-31
• [Patent(Industrial Property Rights)] 抗がん剤感受性の判定方法 (2008)
  • Inventor(s): 谷川原祐介・鈴木小夜・杉本伸二
  • Industrial Property Rights Holder: 学校法人慶應義塾、株式会社ヤクルト
  • Industrial Property Number: 特許, 特願2008-021124号
  • Filing Date: 2008-01-31