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Role of SREBP-1 on the development of hypertesive heart disease

Research Project

Project/Area Number 23500835
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied health science
Research InstitutionUniversity of Tsukuba

Principal Investigator

KUGA Keisuke  筑波大学, 医学医療系, 教授 (60241816)

Co-Investigator(Kenkyū-buntansha) SAKAI Satoshi  筑波大学, 医学医療系, 講師 (30282362)
島野 仁  筑波大学, 医学医療系, 教授 (20251241)
Co-Investigator(Renkei-kenkyūsha) SHIMANO Hitoshi  筑波大学, 医学医療系, 教授 (20251241)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords高血圧 / 線維化 / 炎症反応 / 細胞外マトリックス / 心筋線維化 / ケモカイン / SREBP-1
Research Abstract

We evaluated the role of a transcription factor, SREBP-1, in the development of hypertesive heart disease. We continuously administrated the vasocontractile agent angiotensin II (Ang II) to the SREBP-1-knockout (KO) mice and wild type mice. The wild mice showed the marked fibrous changes around the coronary vasculature in the heart, whereas KO showed the slight changes. We analyzed the alteration of cardiac gene expression by DNA microarray system and confirmed by real-time RT-PCR. The gene groups for extracellular matrix and inflammatory chemokine and cytokine were significantly changed in the wild mice; however, those were suppressed in the KO mice. These findings suggest that SREBP-1 is involved in the development of fibrous changes seen in the hypertensive heart disease.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (33 results)

All 2014 2013 2012 2011 Other

All Journal Article (25 results) (of which Peer Reviewed: 25 results,  Open Access: 4 results) Presentation (8 results)

  • [Journal Article] Stereoselective analysis of flecainide enantiomers using reversed-phase liquid chromatography for assessing CYP2D6 activity.2014

    • Author(s)
      Doki K, Sekiguchi Y, Kuga K, Aonuma K, Kohda Y, Homma M.
    • Journal Title

      Biomed Chromatogr.

      Volume: in press Issue: 9 Pages: 1193-1198

    • DOI

      10.1002/bmc.3143

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endothelin receptor antagonist exacerbates autoimmune myocarditis in mice2014

    • Author(s)
      Tajiri K, Sakai S, Kimura T, Machino-Ohtsuka T, Murakoshi N, Xu D, Wang Z, Sato A, Miyauchi T, Aonuma K
    • Journal Title

      Life Sci

      Volume: (in press) Issue: 2 Pages: 288-296

    • DOI

      10.1016/j.lfs.2014.01.007

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calcitonin gene-related peptide protects the myocardium from ischemia induced by endothelin-1 : Intravital microscopic observation and 31P-MR spectroscopic studies2014

    • Author(s)
      Homma S, Kimura T, Sakai S, Yanagi KI, Miyauchi Y, Aonuma K, Miyauchi T
    • Journal Title

      Life Sci

      Volume: (in press) Issue: 2 Pages: 248-254

    • DOI

      10.1016/j.lfs.2014.02.024

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fish oil constituent eicosapentaenoic acid inhibits endothelin-induced cardiomyocyte hypertrophy via PPAR-α2014

    • Author(s)
      Shimojo N, Jesmin S, Sakai S, Maeda S, Miyauchi T, Mizutani T, Aonuma K, Kawano S
    • Journal Title

      Life Sci

      Volume: (in press) Issue: 2 Pages: 445-7

    • DOI

      10.1016/j.lfs.2014.04.025

    • NAID

      120007130480

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of peptidyl-prolyl isomerase Pin1 in the inhibitory effect of fluvastatin on endothelin-1-induced cardiomyocyte hypertrophy2014

    • Author(s)
      Sakai S, Shimojo N, Kimura T, Tajiri K, Maruyama H, Homma S, Kuga K, Mizutani T, Aonuma K, Miyauchi T
    • Journal Title

      Life Sci

      Volume: 102 Pages: 98-104

    • NAID

      120007136696

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical value of plasma pentraxin 3 levels for predicting cardiac troponin elevation after percutaneous coronary intervention2014

    • Author(s)
      Wang Z, Sato A, Akiyama D, Kimura T, Tajiri K, Hoshi T, Sakai S, Koike A, Miyauchi T, Aonuma K
    • Journal Title

      Life Sci

      Volume: 95 Pages: 40-44

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Feasibility of left ventricular volume measurements by three-dimensional speckle tracking echocardiography depends on image quality and degree of left ventricular enlargement : validation study with cardiac magnetic resonance imaging2014

    • Author(s)
      Kawamura R, Seo Y, Ishizu T, Atsumi A, Yamamoto M, Machino-Ohtsuka T, Nakajima H, Sakai S, Tanaka YO, Minami M, Aonuma K
    • Journal Title

      J Cardiol

      Volume: 63 Pages: 230-238

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel processing system of sterol regulatory element-binding protein-1c regulated by polyunsaturated fatty acid2014

    • Author(s)
      Nakakuki M, Kawano H, Notsu T, Imada K, Mizuguchi K, Shimano H
    • Journal Title

      J Biochem

      Volume: 155 Pages: 301-313

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] SCN5A promoter haplotype affects the therapeutic range for serum flecainide concentration in Asian patients.2014

    • Author(s)
      Doki K, Homma M, Kuga K, Aonuma K, Kohda Y.
    • Journal Title

      Pharmacogenet Genomics.

      Volume: 23 Issue: 7 Pages: 349-354

    • DOI

      10.1097/fpc.0b013e328361fb8d

    • NAID

      120007136378

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of peptidyl-prolyl isomerase Pin1 in the inhibitory effect of fluvastatin on endothelin-1-induced cardiomyocyte hypertrophy.2014

    • Author(s)
      Sakai S, Shimojo N, Kimura T, Tajiri K, Maruyama H, Homma S, Kuga K, Mizutani T, Aonuma K, Miyauchi T.
    • Journal Title

      Life Sci.

      Volume: 102 Issue: 2 Pages: 98-104

    • DOI

      10.1016/j.lfs.2014.03.018

    • NAID

      120007136696

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SCN5A promoter haplotype affects the therapeutic range for serum flecainide concentration in Asian patients2013

    • Author(s)
      Doki K, Homma M, Kuga K, Aonuma K, Kohda Y
    • Journal Title

      Pharmacogenet Genomics

      Volume: 23 Pages: 349-354

    • NAID

      120007136378

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pitavastatin regulates helper T-cell differentiation and ameliorates autoimmune myocarditis in mice2013

    • Author(s)
      Tajiri K, Shimojo N, Sakai S, Machino-Ohtsuka T, Imanaka-Yoshida K, Hiroe M, Tsujimura Y, Kimura T, Sato A, Yasutomi Y, Aonuma K
    • Journal Title

      Cardiovasc Drugs Ther

      Volume: 27 Pages: 413-424

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Negative expression of N-acetylglucosaminyltransferase V in oral squamous cell carcinoma correlates with poor prognosis.2013

    • Author(s)
      Seto K, Uchida F, Baba O, Miyoshi E,et.al.
    • Journal Title

      Springerplus

      Volume: 2 Issue: 1 Pages: 657-657

    • DOI

      10.1186/2193-1801-2-657

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endothelin-1-induced cardiomyocyte hypertrophy is partly regulated by transcription factor II-F interacting C-terminal domain phosphatase of RNA polymeraseII2012

    • Author(s)
      Sakai S, Kimura T, Wang Z, Shimojo N, Maruyama H, Homma S, Kuga K, Yamaguchi I, Aonuma K, Miyauchi T
    • Journal Title

      Life Sci

      Volume: 91 Pages: 572-7

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased plasma levels of big-endothelin-2 and big-endothelin-3 in patients with end-stage renal disease2012

    • Author(s)
      Miyauchi Y, Sakai S, Maeda S, Shimojo N, Watanabe S, Homma S, Kuga K, Aonuma K, Miyauchi T
    • Journal Title

      Life Sci

      Volume: 91 Pages: 729-32

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppressor of cytokine signaling 1 DNA administration inhibits inflammatory and pathogenic responses in autoimmune myocarditis2012

    • Author(s)
      Tajiri K, Imanaka-Yoshida K, Matsubara A, Tsujimura Y, Hiroe M, Naka T, Shimojo N, Sakai S, Aonuma K, Yasutomi Y
    • Journal Title

      J Immunol

      Volume: 189 Pages: 2043-53

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic value of serum tenascin-C levels on long-term outcome after acute myocardial infarction2012

    • Author(s)
      Sato A, Hiroe M, Akiyama D, Hikita H, Nozato T, Hoshi T, Kimura T, Wang Z, Sakai S, Imanaka-Yoshida K, Yoshida T, Aonuma K
    • Journal Title

      J Card Fail

      Volume: 18 Pages: 480-6

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel qualitative aspects of tissue fatty acids related to metabolic regulation : lessons from Elovl6 knockout2012

    • Author(s)
      Shimano H
    • Journal Title

      Prog Lipid Res

      Volume: 51 Pages: 267-71

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Electrocardiographic Determinants of the Polymorphic QRS Morphology in Idiopathic Right Ventricular Outflow Tract Tachycardia2012

    • Author(s)
      Igarashi M, Tada H, Kurosaki K, Yamasaki H, Akiyama D, Sekiguchi Y, Kuroki K, Machino T, Murakoshi N, Nakata Y, Kuga K, Nogami A, Aonuma K
    • Journal Title

      J Cardiovasc Electrophysiol

      Volume: (in press) Issue: 5 Pages: 1881-1888

    • DOI

      10.1111/j.1540-8167.2011.02232.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] CYP2D6 genotype affects age-related decline in flecainide clearance: a population pharmacokinetic analysis2012

    • Author(s)
      Doki K
    • Journal Title

      Pharmacogenet Genomics

      Volume: 22 Issue: 11 Pages: 777-783

    • DOI

      10.1097/fpc.0b013e3283588fe5

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prediction of Chronic Renal Insufficiency after Coronary Angiography by an Early Increase in Oxidative Stress and Decrease in Glomerular Filtration Rate2011

    • Author(s)
      Tajiri K, Maruyama H, Sato A, Shimojo N, Endo M, Aihara H, Kawano S, Watanabe S, Sakai S, Aonuma K
    • Journal Title

      Circ J

      Volume: 75 Pages: 437-442

    • NAID

      10027427336

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of ubiquitin ligase F-box andWD repeat domain-containing 7α (Fbw7α) causes hepatosteatosis through Krueppel-like factor 5 (KLF5)/peroxisome proliferator-activated receptor γ2 (PPARγ2) pathway but not SREBP-1c protein in mice2011

    • Author(s)
      Kumadaki S, Karasawa T, Matsuzaka T, Ema M, Nakagawa Y, Nakakuki M, Saito R, Yahagi N, Iwasaki H, Sone H, Takekoshi K, Yatoh S, Kobayashi K, Takahashi A, Suzuki H, Takahashi S, Yamada N, Shimano H
    • Journal Title

      J Biol Chem

      Volume: 286 Pages: 40835-46

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sterol regulatory element-binding protein-1 determines plasma remnant lipoproteins and accelerates atherosclerosis in low-density lipoprotein receptor-deficient mice2011

    • Author(s)
      Karasawa T, Takahashi A, Saito R, Sekiya M, Igarashi M, Iwasaki H, Miyahara S, Koyasu S, Nakagawa Y, Ishii K, Matsuzaka T, Kobayashi K, Yahagi N, Takekoshi K, Sone H, Yatoh S, Suzuki H, Yamada N, Shimano H
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 31 Pages: 1788-95

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of Chronic Renal Insufficiency After Coronary Angiography by an Early Increase in Oxidative Stress and Decrease in Glomerular Filtration Rate2011

    • Author(s)
      Tajiri K, Sakai K, et al.
    • Journal Title

      Circulation Journal

      Volume: 75 Issue: 2 Pages: 437-442

    • DOI

      10.1253/circj.CJ-10-0622

    • NAID

      10027427336

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sterol regulatory element-binding protein-1 determines plasma remnant lipoproteins and accelerates atherosclerosis in low-density lipoprotein receptor-deficient mice2011

    • Author(s)
      Karasawa T, Takahashi A, Saito R, Sekiya M, Igarashi M, Iwasaki H, Miyahara S, Koyasu S, Nakagawa Y, IshiiK, Matsuzaka T, Kobayashi K, Yahagi N, Takekoshi K, Sone H, Yatoh S, Suzuki H, Yamada N, Shimano H
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 31 Issue: 8 Pages: 1788-95

    • DOI

      10.1161/atvbaha.110.219659

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Elevated Blood Pressure in Resting Daytime‐Phase in A170/SQSTM1‐Knockout Mice, a Newly Established Obese Model2013

    • Author(s)
      Sakai S, Warabi E, Yanagawa T, Kimura T, Tajiri K, Wang Z, Maruyama H, Homma S, Kuga K, Aonuma K, Miyauchi T, Ishii T.
    • Organizer
      13th International Conference on Endothelin
    • Place of Presentation
      筑波大学東京キャンパス(東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Protective Activity to Oxydative Stress is Attenuated in Development of Angiotensin II-Induced Cardiac Fibrosis and Dysfunction2012

    • Author(s)
      Sakai S, Warabi E, Kimura T, Miyauchi T, Aonuma K, Ishii T
    • Organizer
      The 16th Society for Free Radical Research International Biennial Meeting
    • Place of Presentation
      英国ロンドン
    • Year and Date
      2012-09-08
    • Related Report
      2013 Final Research Report
  • [Presentation] Sterol regulatory element-binding protein-1 is involved in the development of angiotensin II-induced cardiac fibrosis2012

    • Author(s)
      Sakai S, Nakagawa N, Shimojo N, Kumura T, Tajiri K, Kuga K, Homma S, Miyauchi T, Aonuma K, Shimano H
    • Organizer
      Basic Cardiovascular Sciences Conference
    • Place of Presentation
      米国ニューオリンズ
    • Year and Date
      2012-07-24
    • Related Report
      2013 Final Research Report
  • [Presentation] Involvement of Sterol Regulatory Element Binding Protein-1 (SREBP-1) in Angiotensin II-Induced Cardiac Injury via Chronic Inflammatory Responses2012

    • Author(s)
      Sakai S, Nakagawa Y, Shimojo N, Kuga K, Homma S, Shimano H, Aonuma K
    • Organizer
      第76回日本循環器学会総会・学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2012-03-06
    • Related Report
      2013 Final Research Report
  • [Presentation] Involvement of Sterol Regulatory Element-binding Protein-1 (SREBP-1) in Angiotensin II-Induced Cardiac Injury via Chronic Inflammatory Responses2012

    • Author(s)
      Sakai S
    • Organizer
      第76回日本循環器学会総会
    • Place of Presentation
      福岡国際会議場( 福岡 )
    • Related Report
      2011 Research-status Report
  • [Presentation] Sterol Regulatory Element-Binding Protein-1 Participates in the Development of Cardiac Injury via Chronic Inflammation2011

    • Author(s)
      Sakai S, Nakagawa Y, Shimojo N, Kuga K, Homma S, Miyauchi T, Shimano H, Aonuma K
    • Organizer
      American Heart Association Scientific Sessions
    • Place of Presentation
      米国オーランド
    • Year and Date
      2011-11-14
    • Related Report
      2013 Final Research Report
  • [Presentation] Slowly Progressed Inflammatory Responses May Contribute to the Angiotensin II-Induced Cardiac Dysfunction2011

    • Author(s)
      Sakai S, Nakagawa Y, Shimojo N, Yoshida K, Kimura T, Maruyama H, Honma S, Shimano H, Aonuma K
    • Organizer
      第75回日本循環器学会総会・学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2011-08-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Sterol regulatory element-binding protein-1 is involved in the development of angiotensin II-induced cardiac fibrosis

    • Author(s)
      Sakai S
    • Organizer
      Basic Cardiovascular Sciences Conference 2012
    • Place of Presentation
      Hilton Hotel (New Orleans, USA)
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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