LDL cholesterol apheresis treatment for arteriosclerosis without hypercholesterolemia

• Project/Area Number: 16K09647
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Yokohama City University
• Principal Investigator: Masato Ohsawa 横浜市立大学, 医学研究科, 客員研究員 (60733433)
• Co-Investigator(Kenkyū-buntansha): 涌井 広道 横浜市立大学, 医学部, 講師 (10587330) ; 戸谷 義幸 横浜市立大学, 附属病院, 准教授 (30237143) ; 田村 功一 横浜市立大学, 医学研究科, 教授 (40285143)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 動脈硬化 / 閉塞性動脈硬化症 / 脂質異常症 / アフェレーシス / レニン・アンジオテンシン系 / 人工透析学 / 腎臓内科学

Outline of Final Research Achievements

Low-density lipoprotein (LDL) apheresis is a potential therapy for conventional therapy resistant peripheral artery disease. We examined the effects of LDL apheresis on clinical parameters in patients who had the complication of peripheral artery disease without hypercholesterolemia in vivo and in vitro and investigate the association the angiotensin receptor-binding molecule and aterosclerosis. Our study showed that leukocyte ATRAP is an emerging marker capable of reflecting the systemic and leukocyte inflammatory profile, and plays a role as an anti-inflammatory factor in the pathophysiology of non-communicable diseases, including hypertension, atherosclerosis and chronic kidney disease (Atherosclerosis. 269:236-244, 2018).

Academic Significance and Societal Importance of the Research Achievements

「正コレステロール血症を呈する従来治療抵抗性閉塞性動脈硬化症に対するデキストラン硫酸カラムを用いたLDLアフェレシス療法」についての、有効性の有無および安全性について多施設共同前向き試験にて症例登録を行い、本療法を受ける患者の血球成分(単球・白血球）検体を用いて検討し、正コレステロール血症を呈する従来治療抵抗性閉塞性動脈硬化症の病態、および本療法の臨床的治療効果とATRAPの関連等について重要な知見を得た。

Research Products

• [Journal Article] Angiotensin receptor-binding molecule in leukocytes in association with the systemic and leukocyte inflammatory profile (2018)
  • Author(s): Haruhara Kotaro、Wakui Hiromichi、Azushima Kengo、Kurotaki Daisuke、Kawase Wataru、Uneda Kazushi、Haku Sona、Kobayashi Ryu、Ohki Kohji、Kinguchi Sho、Ohsawa Masato、Minegishi Shintaro、Ishigami Tomoaki、Matsuda Miyuki、Yamashita Akio、Nakajima Hideaki、Tamura Tomohiko、Tsuboi Nobuo、Yokoo Takashi、Tamura Kouichi
  • Journal Title: Atherosclerosis Volume: 269 Pages: 236-244
  • DOI: 10.1016/j.atherosclerosis.2018.01.013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ATRAP Expression in Brown Adipose Tissue Does Not Influence the Development of Diet-Induced Metabolic Disorders in Mice (2017)
  • Author(s): Wakui H, Ohki K, Azushima K, Uneda K, Haku S, Kobayashi R, Haruhara K, Kinguchi S, Matsuda M, Ohsawa M, Maeda A, Minegishi S, Ishigami T, Toya Y, Yamashita A, Umemura S, Tamura K
  • Journal Title: International Journal of Molecular Sciences Volume: 18 Issue: 3 Pages: 676-676
  • DOI: 10.3390/ijms18030676
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhancement of intrarenal plasma membrane calcium pump isoform 1 expression in chronic angiotensin II-infused mice (2017)
  • Author(s): Wakui Hiromichi、Sumida Koichiro、Fujita Megumi、Ohtomo Yuta、Ohsawa Masato、Kobayashi Ryu、Uneda Kazushi、Azushima Kengo、Haruhara Kotaro、Yatsu Keisuke、Hirawa Nobuhito、Minegishi Shintaro、Ishigami Tomoaki、Umemura Satoshi、Tamura Kouichi
  • Journal Title: Physiological Reports Volume: 5 Issue: 11 Pages: e13316-e13316
  • DOI: 10.14814/phy2.13316
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Angiotensin II Type 1 Receptor‐Associated Protein Regulates Kidney Aging and Lifespan Independent of Angiotensin (2017)
  • Author(s): Uneda Kazushi、Wakui Hiromichi、Maeda Akinobu、Azushima Kengo、Kobayashi Ryu、Haku Sona、Ohki Kohji、Haruhara Kotaro、Kinguchi Sho、Matsuda Miyuki、Ohsawa Masato、Minegishi Shintaro、Ishigami Tomoaki、Toya Yoshiyuki、Atobe Yoshitoshi、Yamashita Akio、Umemura Satoshi、Tamura Kouichi
  • Journal Title: Journal of the American Heart Association Volume: 6 Issue: 8
  • DOI: 10.1161/jaha.117.006120
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 36.Effect of Single-pill Irbesartan/Amlodipine Combination-Based Therapy on Clinic and Home Blood Pressure Profiles in Hypertension with Chronic Kidney Disease (2016)
  • Author(s): Kobayashi R, Tamura K, Wakui H, Ohsawa M, Azushima K, Haku S, Uneda K, Ohki K, Haruhara K, Kinguchi S, Umemura S
  • Journal Title: Clinical and experimental hypertension Volume: 38 Issue: 8 Pages: 744-750
  • DOI: 10.1080/10641963.2016.1200063
  • Peer Reviewed / Open Access
• [Journal Article] 37.Comparison of Direct Renin inhibitor and Angiotensin II Receptor Blocker on Clinic and Ambulatory Blood Pressure Profiles in Hypertension with Chronic Kidney Disease (2016)
  • Author(s): Uneda K, Tamura K, Wakui H, Azushima K, Haku S, Kobayashi R, Ohki K, Haruhara K, Kinguchi S, Ohsawa M, Fujikawa T, Umemura S
  • Journal Title: Clinical and experimental hypertension Volume: 38 Issue: 8 Pages: 738-743
  • DOI: 10.1080/10641963.2016.1200064
  • Peer Reviewed / Open Access
• [Presentation] Predictive usefulness of direct AVF blood flow measurements during the operation by transit-time flowmetry for early AVF failure (2017)
  • Author(s): Masato Ohsawa
  • Organizer: VEITH 2017
  • Int'l Joint Research
• [Presentation] AT1受容体直接結合因子ATRAPのヒト白血球における発現と臨床指標との関連 (2016)
  • Author(s): 春原浩太郎,田村功一,涌井広道,大澤正人,小豆島健護,畝田一司,小林竜,大城光二,金口翔,坪井伸夫,横尾隆,梅村敏
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-06-17