The role of Girdin, a new Akt substrate, in vascular homeostasis

• Project/Area Number: 21790715
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Nagoya University
• Principal Investigator: MAEDA Kengo 名古屋大学, 医学部附属病院, 助教 (80456673)
• Project Period (FY): 2009-04-01 – 2013-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: Girdin / 細胞骨格 / 細胞骨格制御

Research Abstract

The expression of Girdin is found in endothelial cells and vascular smooth muscle cells. We previously found that the expression of Girdin and its Akt-mediated phosphorylation at serine 1416 ragulated the chemotaxis of endothelial cells and played an essential role in angiogenesis. We also found that Girdin formed a complex with R-Ras in mature endothelial cells, where Girdin regulated the intracellular trafficking of VE-cadherin. The results suggest that Girdin regulates transendothelial permmeability in synergy with R-Ras and VE-cadherin.
We additionally investigated the function of Girdin in vascular smooth muscle cells. The expression of Girdin and its Akt-mediated phosphorylation were involeved in the chemotaxis and cytokinesis of vascular smooth muscle cells. Both knockdown of Girdin and knock-in of alanine at serine 1416 attenuated the neointima formation after vascular injury. The results suggest that Girdin is essential for neointimal formation after vascular injury.

Research Products

• [Journal Article] The significance of measuring body fat percentage determined by bioelectrical impedance analysis for detecting subjects with cardiovascular disease risk factors (2012)
  • Author(s): Yamashita K, Kondo T, Osugi S, Shimokata K, Maeda K, Okumura N, Matsudaira K, Shintani S, Muramatsu T, Matsushita K, Murohara T
  • Journal Title: Circ J Volume: 76(10) Pages: 2435-42
  • NAID: 10030875041
  • Peer Reviewed
• [Journal Article] Efficacy and safety of the losartan-hydrochlorothiazide combination tablet in patients with hypertension uncontrolled by angiotensin II receptor antagonist therapy : the Aichi Research on Combination therapy for Hypertension (ARCH) Study (2012)
  • Author(s): Maeda K, Adachi M, Kinoshita A, Koh N, Miura Y, Murohara T
  • Journal Title: Intern Med Volume: 51(10) Pages: 1167-75
  • NAID: 130002062442
  • Peer Reviewed
• [Journal Article] Impact of low levels of vascular endothelial growth factor after myocardial infarction on 6-month clinical outcome. Results from the Nagoya Acute Myocardial Infarction Study (2012)
  • Author(s): Matsudaira K, Maeda K, Okumura N, Yoshikawa D, Morita Y, Mitsuhashi H, Ishii H, Kondo T, Murohara T; Nagoya Acute Myocardial Infarction Study (NAMIS) Group
  • Journal Title: Circ J Volume: 76(6) Pages: 1509-16
  • NAID: 10030316626
  • Peer Reviewed
• [Journal Article] Comparison between valsartan and amlodipine regarding cardiovascular morbidity and mortality in hypertensive patients with glucose intolerance : NAGOYA HEART Study (2012)
  • Author(s): Muramatsu T, Matsushita K, Yamashita K, Kondo T, Maeda K, Shintani S, Ichimiya S, Ohno M, Sone T, Ikeda N, Watarai M, Murohara T; NAGOYA HEART Study Investigators
  • Journal Title: Hypertension Volume: 59(3) Pages: 580-6
  • Peer Reviewed
• [Journal Article] Efficacy and safety of the losartan-hydrochlorothiazide combination tablet in patients with hypertension uncontrolled by angiotensin II receptor antagonist therapy: the Aichi Research on Combination therapy for Hypertension (ARCH) Study. (2012)
  • Author(s): Maeda K
  • Journal Title: Internal Medicine Volume: 51 Pages: 1167-1175
  • NAID: 130002062442
  • Peer Reviewed
• [Journal Article] Impact of Low Levels of Vascular Endothelial Growth Factor After Myocardial Infarction on 6-Month Clinical Outcome (2012)
  • Author(s): Matsudaira K
  • Journal Title: Circulation Journal Volume: 76 Issue: 6 Pages: 1509-1516
  • DOI: 10.1253/circj.CJ-11-1127
  • NAID: 10030316626
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Comparison between valsartan and amlodipine regarding cardiovascular morbidity and mortality in hypertensive patients with glucose intolerance: NAGOYA HEART Study. (2012)
  • Author(s): Muramatsu T
  • Journal Title: Hypertension Volume: 59 Issue: 3 Pages: 580-586
  • DOI: 10.1161/hypertensionaha.111.184226
  • Peer Reviewed
• [Journal Article] Comparison Between Valsartan and Amlodipine Regarding Cardiovascular Morbidity and Mortality in Hypertensive Patients With Glucose Intolerance : NAGOYA HEART Study (2012)
  • Author(s): Muramatsu T
  • Journal Title: Hypertension Volume: 59 Pages: 580-586
  • Peer Reviewed
• [Journal Article] Smoking and smoking cessation in relation to all-cause mortality and cardiovascular events in 25, 464 healthy male Japanese workers (2011)
  • Author(s): Kondo T, Osugi S, Shimokata K, Honjo H, Morita Y, Maeda K, Yamashita K, Muramatsu T, Shintani S, Matsushita K, Murohara T
  • Journal Title: Circ J Volume: 75(12) Pages: 2885-92
  • NAID: 10030033623
  • Peer Reviewed
• [Journal Article] Metabolic syndrome and all-cause mortality, cardiac events, and cardiovascular events : a follow-up study in 25, 471 young- and middle-aged Japanese men (2011)
  • Author(s): Kondo T, Osugi S, Shimokata K, Honjo H, Morita Y, Yamashita K, Maeda K, Muramatsu T, Shintani S, Matsushita K, Murohara T
  • Journal Title: Eur J Cardiovasc Prev Rehabil Volume: 18(4) Pages: 574-80
  • Peer Reviewed
• [Journal Article] The actin-binding protein Girdin and its Akt-mediated phosphorylation regulate neointima formation after vascular injury (2011)
  • Author(s): Miyake H, Maeda K, Asai N, Shibata R, Ichimiya H, Isotani-Sakakibara M, Yamamura Y, Kato K, Enomoto A, Takahashi M, Murohara T
  • Journal Title: Circ Res Volume: 108(10) Pages: 1170-9
  • Peer Reviewed
• [Journal Article] Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cells (2011)
  • Author(s): Matsushita E, Asai N, Enomoto A, Kawamoto Y, Kato T, Mii S, Maeda K, Shibata R, Hattori S, Hagikura M, Takahashi K, Sokabe M, Murakumo Y, Murohara T, Takahashi M
  • Journal Title: Mol Biol Cell Volume: 22(6) Pages: 736-47
  • Peer Reviewed
• [Journal Article] The actin-binding protein Girdin and its Akt-mediated phosphorylation regulate neointima formation after vascular injury. (2011)
  • Author(s): Miyake H
  • Journal Title: Circulation Research Volume: 108 Issue: 10 Pages: 1170-1179
  • DOI: 10.1161/circresaha.110.236174
  • Peer Reviewed
• [Journal Article] The actin-binding protein Girdin and its Akt-mediated phosphorylation regulate neointima formation after vascular injury (2011)
  • Author(s): Miyake H
  • Journal Title: Circ Res Volume: 108 Pages: 1170-1179
  • Peer Reviewed
• [Journal Article] Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cells (2011)
  • Author(s): Matsushita E
  • Journal Title: Mol Biol Cell Volume: 22 Pages: 736-747
  • Peer Reviewed
• [Journal Article] Protective Role of Gipie, a Girdin Family Protein, in Endoplasmic Reticulum Stress Responses in Endothelial Cells. (2011)
  • Author(s): Matsushita E
  • Journal Title: Mol Biol Cell. Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Rationale and design of the NAGOYA HEART Study : comparison between valsartan and amlodipine regarding morbidity and mortality in patients with hypertension and glucose intolerance (2010)
  • Author(s): Matsushita K, Muramatsu T, Kondo T, Maeda K, Shintani S, Murohara T; NAGOYA HEART Study Group
  • Journal Title: J Cardiol Volume: 56(1) Pages: 111-7
  • NAID: 10027703831
  • Peer Reviewed
• [Journal Article] Pitavastatin, an HMG-CoA reductase inhibitor, ameliorates endothelial function in chronic smokers (2010)
  • Author(s): Yoshida O, Kondo T, Kureishi-Bando Y, Sugiura T, Maeda K, Okumura K, Murohara T
  • Journal Title: Circ J Volume: 74(1) Pages: 195-202
  • NAID: 10025941804
  • Peer Reviewed
• [Journal Article] Rationale and design of the NAGOYA HEART Study : comparison between valsartan and amlodipine regarding morbidity and mortality in patients with hypertension and glucose intolerance. (2010)
  • Author(s): Matsushita K
  • Journal Title: J Cardiol. Volume: 56 Pages: 111-117
  • Peer Reviewed
• [Journal Article] Pitavastatin, an HMG-CoA reductase inhibitor, ameliorates endothelial function in chronic smokers. (2010)
  • Author(s): Yoshida O
  • Journal Title: Circ J. Volume: 74 Pages: 195-202
  • Peer Reviewed
• [Presentation] Actin binding protein Girdin/Ccdc88a regulates vascular permeability via interaction with Rras (2011)
  • Author(s): Kengo Maeda, Hitoshi Ichimiya1, Hiroshi Miyake, Atsushi Enomoto, Masahide Takahashi, Toyoaki Murohara
  • Organizer: 日本循環器学会総会
  • Place of Presentation: パシフィコ横浜 横浜市
  • Year and Date: 2011-08-03
• [Presentation] Actin binding protein Girdin/Ccdc88a regulates vascular permeability via interaction with Rras (2011)
  • Author(s): 前田健吾
  • Organizer: 日本循環器学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-08-03
• [Presentation] Akt/PKB Substrate Girdin Has an Impact on the Neointimal Formation by Regulating Migration and Proliferation of VSMCs (2010)
  • Author(s): Hiroshi Miyake, Kengo Maeda,Tomoya Kitamura1, Rei Shibata1,Atsushi Enomoto, Masahide Takahashi, Toyoaki Murohara
  • Organizer: 日本循環器学会総会
  • Place of Presentation: 京都国際会議場 京都市
  • Year and Date: 2010-03-07
• [Presentation] 新規Akt基質 Girdinによる血管新生の制御 (2009)
  • Author(s): 前田 健吾
  • Organizer: 第50回日本脈管学会総会 シンポジウム 2循環器内科系 内皮と脈管疾患
  • Place of Presentation: ハイアットリージェンシー東京 東京都
  • Year and Date: 2009-10-29