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Impact of integrin on the development of aortic dissection

Research Project

Project/Area Number 18K08758
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55030:Cardiovascular surgery-related
Research InstitutionOkayama University

Principal Investigator

MIYOSHI Toru  岡山大学, 大学病院, 講師 (70444651)

Co-Investigator(Kenkyū-buntansha) 中村 一文  岡山大学, 医歯薬学総合研究科, 准教授 (10335630)
米澤 朋子  岡山大学, 医歯薬学総合研究科, 助教 (30304299)
吉田 賢司  岡山大学, 医歯薬学総合研究科, 講師 (70532761)
伊藤 浩  岡山大学, 医歯薬学総合研究科, 教授 (90446047)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords大動脈解離 / インテグリン / アンジオテンシン / 細胞外マトリックス / 胸部大動脈解離 / α1インテグリン / 血管平滑筋細胞 / 線維芽細胞 / 腹部大動脈瘤 / マイクロアレイ
Outline of Final Research Achievements

For animal experiments, aortic dissection model was made by subcutaneous infusion of lysyl oxidase inhibitor and angiotensin II. The incidence of aortic dissection in integrin α1 Knockout (Itga1KO) mice was significantly reduced compared with control mice. These results suggests that Itga1 play an important role in the development of aortic dissection. Next, the differences in mRNA expressions between Itga1 KO mice and control mice of aortic dissection model were evaluated by real-time quantitative PCR. The mRNA expressions of inflammatory genes and matrix matrix metalloproteinase in Itga1 KO mice were significantly lower than those in control mice. Taken together, Itga1 may be crucial for the development of aortic dissection.

Academic Significance and Societal Importance of the Research Achievements

胸部大動脈解離は大動脈中膜が突然破断する疾患であるが、その病態はほとんど解明されていない。そのため、その解離の予測は困難であり、いったん発症すると高い致命率となる。血管の中膜には血管平滑筋細胞、線維芽細胞があるが、その強度の維持にはエラスチンをはじめとする細胞外マトリックスが重要な役割を果たす。細胞はインテグリンを細胞外マトリックスと繋がり、活性化や抑制の制御を受けることが知られている。本研究で、マウスモデルではα1インテグリンの欠損が大動脈解離発症を抑制することが示された。インテグリンを介した大動脈解離発症抑制の新たな治療戦略に寄与する可能性が示唆された。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (27 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 11 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Cardio-Ankle Vascular Index and Atrial Remodeling for Atrial Fibrillation2021

    • Author(s)
      Miyoshi T
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 28 Issue: 6 Pages: 584-585

    • DOI

      10.5551/jat.ED148

    • NAID

      130008046575

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2021-06-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Higher oxidized high-density lipoprotein to apolipoprotein A-I ratio is associated with high-risk coronary plaque characteristics determined by CT angiography2021

    • Author(s)
      Suruga K, Miyoshi T, Kotani K, Ichikawa K, Miki T, Osawa K, Ejiri K, Toda H, Nakamura K, Morita H, Ito H
    • Journal Title

      Int J Cardiol

      Volume: 324 Pages: 193-198

    • DOI

      10.1016/j.ijcard.2020.09.060

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prognostic Value of Coronary Computed Tomographic Angiography in Patients With Nonalcoholic Fatty Liver Disease2020

    • Author(s)
      Ichikawa K, Miyoshi T, Osawa K, Miki T, Nakamura K, Ito H
    • Journal Title

      JACC Cardiovasc Imaging

      Volume: 13(7) Issue: 7 Pages: 1628-1630

    • DOI

      10.1016/j.jcmg.2020.01.022

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improvement in renal and endothelial function after catheter ablation in patients with persistent atrial fibrillation2020

    • Author(s)
      Okawa K, Miyoshi T, Sogo M, Hara S, Sudo Y, Ugawa S, Takahashi M, Doi M, Morita H, Ito H
    • Journal Title

      J Cardiol

      Volume: 76(6) Issue: 6 Pages: 610-617

    • DOI

      10.1016/j.jjcc.2020.07.002

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deficiency of CD44 prevents thoracic aortic dissection in a murine model.2020

    • Author(s)
      Hatipoglu OF, Miyoshi T, Yonezawa T, Kondo M, Amioka N, Yoshida M, Akagi S, Nakamura K, Hirohata S, Ito H.
    • Journal Title

      Sci Rep

      Volume: 10 Issue: 1 Pages: 6869-6869

    • DOI

      10.1038/s41598-020-63824-9

    • NAID

      120006883500

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Switching to Azilsartan From Fixed-Dose Combination of an Angiotensin II Receptor Blocker and Calcium Channel Blocker or a Thiazide in Patients With Hypertension.2019

    • Author(s)
      Miyoshi T, Onoue G, Ito H.
    • Journal Title

      J Clin Med Res.

      Volume: 11(3) Issue: 3 Pages: 202-207

    • DOI

      10.14740/jocmr3723

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Brachial intima-media thickness is associated with coronary artery atherosclerosis in patients with diabetes mellitus.2019

    • Author(s)
      Ono T, Miyoshi T, Ohno Y, Osawa K, Takaya Y, Miki T, Ichikawa K, Ito H.
    • Journal Title

      Heart Vessels.

      Volume: 34(9) Issue: 9 Pages: 1405-1411

    • DOI

      10.1007/s00380-019-01371-8

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emerging Role of Coronary Computed Tomography Angiography in Lipid-Lowering Therapy: a Bridge to Image-Guided Personalized Medicine.2019

    • Author(s)
      Miyoshi T, Osawa K, Ichikawa K, Suruga K, Miki T, Yoshida M, Nakagawa K, Toda H, Nakamura K, Morita H, Ito H.
    • Journal Title

      Curr Cardiol Rep.

      Volume: 21(8) Issue: 8 Pages: 72-72

    • DOI

      10.1007/s11886-019-1170-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum malondialdehyde-modified low-density lipoprotein levels on admission predict prognosis in patients with acute coronary syndrome undergoing percutaneous coronary intervention.2019

    • Author(s)
      Amioka N , Miyoshi T , Otsuka H , Yamada D , Takaishi A , Ueeda M , Hirohata S , Ito H.
    • Journal Title

      J Cardiol.

      Volume: S0914-5087(19) Issue: 3 Pages: 30051-6

    • DOI

      10.1016/j.jjcc.2019.02.012

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decrease in oxidized high-density lipoprotein is associated with slowed progression of coronary artery calcification: Subanalysis of a prospective multicenter study.2019

    • Author(s)
      Miki T, Miyoshi T, Kotani K, et al.
    • Journal Title

      Atherosclerosis

      Volume: - Pages: 1-6

    • DOI

      10.1016/j.atherosclerosis.2019.01.032

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of LCZ696, a dual angiotensin receptor neprilysin inhibitor, on isoproterenol-induced cardiac hypertrophy, fibrosis, and hemodynamic change in rats.2019

    • Author(s)
      Miyoshi T, Nakamura K, Miura D, Yoshida M, Saito Y, Akagi S, Ohno Y, Kondo M, Ito H.
    • Journal Title

      Cardiol J.

      Volume: 26(5) Issue: 5 Pages: 575-583

    • DOI

      10.5603/cj.a2018.0048

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diastolic Dysfunction Is a Risk of Perioperative Myocardial Injury Assessed by High-Sensitivity Cardiac Troponin T in Elderly Patients Undergoing Non-Cardiac Surgery2018

    • Author(s)
      Toda H, Nakamura K, Nakagawa K, Watanabe A, Miyoshi T, Nishii N, Shimizu K,
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 3 Pages: 775-782

    • DOI

      10.1253/circj.CJ-17-0747

    • NAID

      130006394516

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of Intensive and Standard Pitavastatin Treatment With or Without Eicosapentaenoic Acid on Progression of Coronary Artery Calcification Over 12 Months ― Prospective Multicenter Study ―2018

    • Author(s)
      Miyoshi T, Kohno K, Asonuma H, Sakuragi S, Nakahama M, Kawai Y, Uesugi Oka T, Munemasa M, Takahashi N, Mukohara N, Habara S, Koyama Y, Nakamura K, Ito H; PEACH Investigators.T,
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 2 Pages: 532-540

    • DOI

      10.1253/circj.CJ-17-0419

    • NAID

      130006320291

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical Applications of Three-Dimensional Printing in Cardiovascular Disease2018

    • Author(s)
      Akira Kurata, Yasushi Koyama, Takashi Shirakawa, Toru Miyoshi
    • Journal Title

      CVIA

      Volume: 2 Pages: 153-165

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 接着分子CD44の機能制御と大動脈瘤・大動脈解離における役割2020

    • Author(s)
      Omer F. Hatipoglu、三好 亨
    • Organizer
      第49回日本心脈管作動物質学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] FFR-CT as a Practical Tool in Optimizing PCI Strategy2020

    • Author(s)
      Toru Miyoshi
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Pemafibrate Reduces the Rupture of Experimental Aortic Aneurysm by Inhibiting Oxidative Stress2020

    • Author(s)
      Naofumi Amioka, Toru Miyoshi, Tomonari Kimura, Satoshi Akagi, Masashi Yoshida, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Itoh
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Higher Oxidized HDL is Associated with High-risk Plaques Determined by CT Angiography in Patients with Suspected with Coronary Artery Disease2020

    • Author(s)
      Kazuki Suruga, Toru Miyoshi, Kazuhiko Kotani, Takashi Miki, Keishi Ichikawa, Kazuhiro Osawa, Hiroaki Otsuka, Masatoki Yoshida, Kazufumi Nakamura, Hiroshi Itoh
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Efficacy of Digitalis on Heart Failure with Reduced Ejection Fraction and Sinus Tachycardia under Administration of More than Two Catecholamines2020

    • Author(s)
      Toru Miyoshi, Tomohito Ohtani, Kei Nakamoto, Isamu Mizote, Yasuharu Takeda, Shungo Hikosoh, Yasushi Sakata
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Impact of Zero Coronary Artery Calcium Score on Favorable Prognosis in Nonalcoholic Fatty Liver Disease Patients2020

    • Author(s)
      Keishi Ichikawa, Toru Miyoshi, Takashi Miki, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Itoh
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] CD44 is Associated with the Development of Thoracic Aortic Aneurysm and Dissection in Mice2019

    • Author(s)
      Toru Miyoshi 、Kazufumi Nakamura 、Masashi Yoshida 、Satoshi Akagi 、Tomonari Kimura 、Naofumi Amioka 、Hiroshi Itoh
    • Organizer
      第 83 回日本循環器学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Deficiency of Integrin Alpha1 Prevents Abdominal Aortic Aneurysm Rupture in Mice2019

    • Author(s)
      Toru Miyoshi 、Kazufumi Nakamura 、Masashi Yoshida 、Satoshi Akagi 、Tomonari Kimura 、Naofumi Amioka 、Hiroshi Itoh
    • Organizer
      第 83 回日本循環器学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] High Baseline Lipoprotein(a) Level as a Risk Factor For Coronary Artery Calcification Progression: Sub-analysis of a Prospective Multicenter Trial2018

    • Author(s)
      Toru Miyoshi, Masayuki Doi, Hiroshi Ito, on behalf of PEACH investigators
    • Organizer
      EAS2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 心血管イベントの危険因子としてのNAFLD : CTからの考察2018

    • Author(s)
      三好 亨、大澤和宏、伊藤 浩
    • Organizer
      第50回日本動脈硬化学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Incremental prognostic value of cardio-ankle vascular index as an arterial stiffness marker in patients with intermediate risk for cardiovascular disease2018

    • Author(s)
      Tamaki Ono, Toru Miyoshi, Yuko Ohno, K kuroda, G. Shokoku, K Yamamoto, K Tokioka, Y Kawai, Hiroshi Ito
    • Organizer
      ESC2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Critical Role of CD44 in the Development of Thoracic Aortic Aneurysm and Dissection in Mice2018

    • Author(s)
      Toru Miyoshi, Omer Hatipoglu, Megumi Kondo, Kazufumi Nakamura, Hiroshi Ito
    • Organizer
      AHA2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] 循環器内科グリーンノート2018

    • Author(s)
      三好 亨
    • Total Pages
      540
    • Publisher
      中外医学社
    • ISBN
      9784498134263
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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