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

• Project/Area Number: 23500835
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: University 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: ¥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.

Research Products

• [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
  • Peer Reviewed
• [Journal Article] Endothelin receptor antagonist exacerbates autoimmune myocarditis in mice (2014)
  • 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
  • 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 studies (2014)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Fish oil constituent eicosapentaenoic acid inhibits endothelin-induced cardiomyocyte hypertrophy via PPAR-α (2014)
  • 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
  • Peer Reviewed / Open Access
• [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 Pages: 98-104
  • NAID: 120007136696
  • Peer Reviewed
• [Journal Article] Clinical value of plasma pentraxin 3 levels for predicting cardiac troponin elevation after percutaneous coronary intervention (2014)
  • 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
  • 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 imaging (2014)
  • 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
  • Peer Reviewed
• [Journal Article] A novel processing system of sterol regulatory element-binding protein-1c regulated by polyunsaturated fatty acid (2014)
  • Author(s): Nakakuki M, Kawano H, Notsu T, Imada K, Mizuguchi K, Shimano H
  • Journal Title: J Biochem Volume: 155 Pages: 301-313
  • 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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] SCN5A promoter haplotype affects the therapeutic range for serum flecainide concentration in Asian patients (2013)
  • Author(s): Doki K, Homma M, Kuga K, Aonuma K, Kohda Y
  • Journal Title: Pharmacogenet Genomics Volume: 23 Pages: 349-354
  • NAID: 120007136378
  • Peer Reviewed
• [Journal Article] Pitavastatin regulates helper T-cell differentiation and ameliorates autoimmune myocarditis in mice (2013)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Endothelin-1-induced cardiomyocyte hypertrophy is partly regulated by transcription factor II-F interacting C-terminal domain phosphatase of RNA polymeraseII (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Increased plasma levels of big-endothelin-2 and big-endothelin-3 in patients with end-stage renal disease (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Suppressor of cytokine signaling 1 DNA administration inhibits inflammatory and pathogenic responses in autoimmune myocarditis (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Prognostic value of serum tenascin-C levels on long-term outcome after acute myocardial infarction (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Novel qualitative aspects of tissue fatty acids related to metabolic regulation : lessons from Elovl6 knockout (2012)
  • Author(s): Shimano H
  • Journal Title: Prog Lipid Res Volume: 51 Pages: 267-71
  • Peer Reviewed
• [Journal Article] Electrocardiographic Determinants of the Polymorphic QRS Morphology in Idiopathic Right Ventricular Outflow Tract Tachycardia (2012)
  • 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
  • Peer Reviewed
• [Journal Article] CYP2D6 genotype affects age-related decline in flecainide clearance: a population pharmacokinetic analysis (2012)
  • Author(s): Doki K
  • Journal Title: Pharmacogenet Genomics Volume: 22 Issue: 11 Pages: 777-783
  • DOI: 10.1097/fpc.0b013e3283588fe5
  • Peer Reviewed
• [Journal Article] Prediction of Chronic Renal Insufficiency after Coronary Angiography by an Early Increase in Oxidative Stress and Decrease in Glomerular Filtration Rate (2011)
  • 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
  • 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 mice (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Sterol regulatory element-binding protein-1 determines plasma remnant lipoproteins and accelerates atherosclerosis in low-density lipoprotein receptor-deficient mice (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Prediction of Chronic Renal Insufficiency After Coronary Angiography by an Early Increase in Oxidative Stress and Decrease in Glomerular Filtration Rate (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Sterol regulatory element-binding protein-1 determines plasma remnant lipoproteins and accelerates atherosclerosis in low-density lipoprotein receptor-deficient mice (2011)
  • 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
  • Peer Reviewed
• [Presentation] Elevated Blood Pressure in Resting Daytime‐Phase in A170/SQSTM1‐Knockout Mice, a Newly Established Obese Model (2013)
  • 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）
• [Presentation] Protective Activity to Oxydative Stress is Attenuated in Development of Angiotensin II-Induced Cardiac Fibrosis and Dysfunction (2012)
  • 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
• [Presentation] Sterol regulatory element-binding protein-1 is involved in the development of angiotensin II-induced cardiac fibrosis (2012)
  • 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
• [Presentation] Involvement of Sterol Regulatory Element Binding Protein-1 (SREBP-1) in Angiotensin II-Induced Cardiac Injury via Chronic Inflammatory Responses (2012)
  • 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
• [Presentation] Involvement of Sterol Regulatory Element-binding Protein-1 (SREBP-1) in Angiotensin II-Induced Cardiac Injury via Chronic Inflammatory Responses (2012)
  • 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 ）
• [Presentation] Sterol Regulatory Element-Binding Protein-1 Participates in the Development of Cardiac Injury via Chronic Inflammation (2011)
  • 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
• [Presentation] Slowly Progressed Inflammatory Responses May Contribute to the Angiotensin II-Induced Cardiac Dysfunction (2011)
  • 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
• [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)