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Pathological clarification of thrombosis risk related to homocysteine interacted with lipoprotein vitamin E and lipoprotein (a)

Research Project

Project/Area Number 17K09560
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionJikei University School of Medicine

Principal Investigator

Yoshida Hiroshi  東京慈恵会医科大学, 医学部, 教授 (30333529)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsLp(a) / ホモシステイン / 腎機能 / 2型糖尿病 / リポ蛋白(a) / ビタミンB群 / 亜鉛 / 慢性腎臓病 / 尿酸 / Lp(a) / Nrf2 / 糖尿病腎症 / マクロファージ / 血栓性動脈硬化症 / 腎臓病合併症 / 血栓リスク / 臨床血管学
Outline of Final Research Achievements

To address the research subject, "Pathological clarification of thrombosis risk related to homocysteine interacted with lipoprotein vitamin E and lipoprotein (a) [Lp(a)]", the association between homocysteine and Lp(a), both of which may be involved in the thrombosis risk, was investigated at first in patients with type 2 diabetes. But, the association between the two was not found at all.
However, eGFR, kidney function, folic acid, and vitamin B12 significantly correlated with homocysteine independently of gender, age, BMI, and glucose control status (HbA1c). Furthermore, multivariate regression analyses showed the significant association of Lp(a) with eGFR and BMI. This association was found markedly in the study subjects without statin therapy.
Therefore, serum levels of homocysteine and Lp(a) for the atherothrombotic risk should be presumably investigated in diabetic patients with renal dysfunction especially in terms of nutritional status and statin therapy.

Academic Significance and Societal Importance of the Research Achievements

2型糖尿病患者では、非糖尿病患者に比べて血中ホモシステイン濃度が高いことが認められているほか、糖尿病腎症患者では、CKDを合併していない糖尿病患者よりも血中ホモシステイン濃度が高いこと、血清ホモシステイン濃度は糖尿病腎症のリスクと重症度に関連することが報告されているが、ビタミンB12や葉酸の栄養管理により、腎症を有する2型糖尿病患者にいおいても動脈硬化・血栓疾患と関連するホモシステインをコントロールできる可能性が示唆された。また動脈硬化危険因子であるLp(a)とeGFRに独立した負の相関がみられるが、スタチンの使用と不使用で違いがあることは2型糖尿病の診療のなかで留意すべきある。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (31 results)

All 2021 2020 2019 2018 2017

All Journal Article (13 results) (of which Peer Reviewed: 12 results,  Open Access: 2 results) Presentation (18 results) (of which Invited: 8 results)

  • [Journal Article] Secondary dyslipidemia: its treatments and association with atherosclerosis2021

    • Author(s)
      Yanai H, Yoshida H.
    • Journal Title

      Global Health & Medicine

      Volume: 3 Issue: 1 Pages: 15-23

    • DOI

      10.35772/ghm.2020.01078

    • NAID

      130007999111

    • ISSN
      2434-9186, 2434-9194
    • Year and Date
      2021-02-28
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relations between urinary albumin excretion and a dietary intake of fruits in patients with type 2 diabetes.2021

    • Author(s)
      Matsui S, Someya Y, Yoshida H
    • Journal Title

      J Clin Med Res

      Volume: 13 Issue: 3 Pages: 151-157

    • DOI

      10.14740/jocmr4440

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Verification of low-density lipoprotein cholesterol levels measured by anion-exchange high performance liquid chromatography in comparison with beta quantification reference measurement procedure.2021

    • Author(s)
      Manita D, Yoshida H, Koyama I, Nakamura M, Hirowatari Y.
    • Journal Title

      J Appl Lab Med

      Volume: 6 Issue: 3 Pages: 654-667

    • DOI

      10.1093/jalm/jfaa144

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reference Intervals of Serum Non-Cholesterol Sterols by Gender in Healthy Japanese Individuals2020

    • Author(s)
      Hiroshi Yoshida, Hayato Tada, Kumie Ito, Yoshimi Kishimoto, Hidekatsu Yanai, Hideaki Bujo, Tomonori Okamura, Katsunori Ikewaki, Tetsuo Shoji, Takashi Miida, Masayuki Yoshida, Masafumi Kuzuya, Shizuya Yamashita.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 27 Issue: 5 Pages: 409-417

    • DOI

      10.5551/jat.50187

    • NAID

      130007839063

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2020-05-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Diagnostic Criteria 2020 for Triglyceride Deposit Cardiomyovasculopathy2020

    • Author(s)
      Kobayashi K, Sakata Y, Miyauchi H, Ikeda Y, Nagasawa Y, Nakajima K, Shimada K, Kozawa J, Hao H, Amano T, Yoshida H, Inaba T, Hashimoto C, Hirano K, for the Japan TGCV Study Group.
    • Journal Title

      Annals of Nuclear Cardiology

      Volume: 6 Issue: 1 Pages: 99-104

    • DOI

      10.17996/anc.20-00131

    • NAID

      130007893671

    • ISSN
      2189-3926, 2424-1741
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Innovatively Established Analysis Method for Lipoprotein Profiles Based on High-Performance Anion-Exchange Liquid Chromatography2019

    • Author(s)
      Hirowatari Y, Yoshida H.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 26 Issue: 12 Pages: 1027-1040

    • DOI

      10.5551/jat.RV17037

    • NAID

      130007754429

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2019-12-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical Impact and Significance of Serum Lipoprotein (a) Levels on Cardiovascular Risk in Patients With Coronary Artery Disease2019

    • Author(s)
      Yoshida Hiroshi
    • Journal Title

      Circulation Journal

      Volume: 83 Issue: 5 Pages: 967-968

    • DOI

      10.1253/circj.CJ-19-0221

    • NAID

      130007636987

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2019-04-25
    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A new method for measuring cholesterol efflux capacity uses stable isotope-labeled, not radioactive-labeled, cholesterol.2019

    • Author(s)
      1)Shimizu T, Miyazaki O, Iwamoto T, Usui T, Sato R, Hiraishi C, Yoshida H.
    • Journal Title

      J Lipid Res

      Volume: 60 Issue: 11 Pages: 1959-1967

    • DOI

      10.1194/jlr.d086884

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Beneficial Effects of Adiponectin on Glucose and Lipid Metabolism and Atherosclerotic Progression: Mechanisms and Perspectives2019

    • Author(s)
      Yanai Hidekatsu、Yoshida Hiroshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 5 Pages: 1190-1190

    • DOI

      10.3390/ijms20051190

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 高Lp(a)血症の診断の問題点と治療の展望.2019

    • Author(s)
      吉田博、越智小枝
    • Journal Title

      Heart View

      Volume: 23 Pages: 774-780

    • Related Report
      2019 Research-status Report
  • [Journal Article] An Intriguing and Important Concept Relevant to Oxidized Low-Density Lipoprotein and Atherogenesis is Still Problematic for its Contribution to the Better Understanding of Clinical Atherosclerosis2018

    • Author(s)
      Yoshida Hiroshi
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 25 Issue: 10 Pages: 1007-1008

    • DOI

      10.5551/jat.ED101

    • NAID

      130007490684

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2018-10-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of angiotensin II on matrix metalloproteinase-2 secretion in human umbilical vein endothelial cells.2018

    • Author(s)
      Sato R, Hiraishi C, Yoshida H.
    • Journal Title

      J Cardiovasc Pharmacology

      Volume: 71 Issue: 4 Pages: 233-239

    • DOI

      10.1097/fjc.0000000000000564

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cholesterol Levels of Six Fractionated Serum Lipoproteins and its Relevance to Coronary Heart Disease Risk Scores2017

    • Author(s)
      Manita D, Yoshida H, Hirowatari Y.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 24 Issue: 9 Pages: 928-939

    • DOI

      10.5551/jat.34728

    • NAID

      130006038522

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 動脈硬化性心血管疾患の残余リスクの再考と非空腹時トリグリセライド2021

    • Author(s)
      吉田博
    • Organizer
      第21回動脈硬化教育フォーラム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Lp(a)の臨床的意義に関するアップデート2020

    • Author(s)
      吉田博
    • Organizer
      第60回日本臨床化学会年次学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] アスタキサンチン処理によるマウス・マクロファージ株細胞におけるNrf2関連酸化ストレス防衛機構の影響2020

    • Author(s)
      佐藤亮、鈴木亮平、長谷川智子、吉田博
    • Organizer
      第60回日本臨床化学会年次学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 尿沈査スコアと尿中NGALとの関連性2020

    • Author(s)
      佐藤亮、堀口久孝、齊藤正二、長谷川智子、吉田博
    • Organizer
      第67回日本臨床検査医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 明らかな腎機能異常がない2型糖尿病患者における腎機能の程度と血清ホモシステインの関連性2020

    • Author(s)
      平石千佳、松井貞子、小島貴衣、長谷川智子、藤本啓、吉田博
    • Organizer
      第27回日本未病学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 積極的脂質低下療法の新たなエビデンス.LDLコレステロールの次なる治療ターゲットと残余リスクの評価.2019

    • Author(s)
      吉田博
    • Organizer
      第51回日本動脈硬化学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] ハイリスク患者に対する脂質管理のあり方.残余リスクとLp(a).2019

    • Author(s)
      吉田博
    • Organizer
      第51回日本動脈硬化学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 安定同位体を用いたコレステロール引き抜き能評価系の検討 第2報.2019

    • Author(s)
      清水知、宮崎修、吉田博
    • Organizer
      第59回日本臨床化学会年次学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 高齢2型糖尿病患者における腎機能障害評価因子の検討.2019

    • Author(s)
      7)平石千佳、松井貞子、小島貴衣、佐藤亮、藤本啓、吉田博
    • Organizer
      第26回日本未病システム学会
    • Related Report
      2019 Research-status Report
  • [Presentation] アスタキサンチン処理によるマウス・マクロファージ株細胞におけるNrf2関連酸化ストレス防衛機構の影響.2019

    • Author(s)
      5)佐藤亮、山川奈菜子、堀口久孝、齊藤正二、長谷川智子、吉田博
    • Organizer
      第66回日本臨床検査医学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 臨床検査から見た高齢者腎臓病の評価2018

    • Author(s)
      平石千佳、吉田 博、小峯直彦、長谷川智子、藤本 啓
    • Organizer
      第61回日本糖尿病学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 動脈硬化性疾患リスク因子Lp(a)の構造と代謝2018

    • Author(s)
      吉田 博
    • Organizer
      第50回日本動脈硬化学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 健康長寿と歩む未病へのアプローチ~脂質異常症と動脈硬化の視座から~2018

    • Author(s)
      吉田 博
    • Organizer
      第25回日本未病システム学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 女性の減量ダイエットによる各リポ蛋白のコレステロールおよびαトコフェロールへの影響2018

    • Author(s)
      佐藤 亮、大原布由美、平石千佳、真仁田大輔、廣渡祐史、田中 明、吉田 博
    • Organizer
      第65回日本臨床検査医学会・学術
    • Related Report
      2018 Research-status Report
  • [Presentation] 全自動化学発光免疫測定装置(ARCHITECT)を用いた尿中NGALの院内実施に向けた基礎的検討2018

    • Author(s)
      小島貴衣、鈴木亮平、鶴川治美、佐藤 亮、菱木光太郎、堀口久孝、齊藤正二、長谷川智子、平石千佳、吉田 博
    • Organizer
      第65回日本臨床検査医学会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] シンポジウム13.冠動脈疾患のリスク抑制に貢献するLp(a)低下の期待.2017

    • Author(s)
      吉田 博
    • Organizer
      第65回日本心臓病学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 明日へのシンポジウム2.脂質異常症診療のupdate.再び注目されるリスクファクター Lp(a).2017

    • Author(s)
      吉田 博
    • Organizer
      第49回日本動脈硬化学会
    • Related Report
      2017 Research-status Report
  • [Presentation] リポ蛋白プロファイルと腎機能ならびに吹田スコアに関する健常者群と疾患群の比較.2017

    • Author(s)
      真仁田大輔、佐藤 亮、吉田 博、廣渡祐史.
    • Organizer
      第57回日本臨床化学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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