Investigation of new vasoactive peptides as risk/biomarker for coronary atherosclerosis

• Project/Area Number: 26460659
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Watanabe Takuya 東京薬科大学, 生命科学部, 教授 (30297014)
• Co-Investigator(Kenkyū-buntansha): 木庭 新治 昭和大学, 医学部, 准教授 (20276546) ; 礒 良崇 昭和大学, 大学共同利用機関等の部局等, 准教授 (60384244) ; 佐藤 健吾 東京薬科大学, 生命科学部, 助教 (70549930)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 動脈硬化 / 冠動脈疾患 / ペプチド / バイオマーカー / 創薬 / リスクファクター

Outline of Final Research Achievements

The present study (cellular, animal, and clinical research) provides the first evidence to demonstrate that new vasoactive peptides regulate atherosclerosis. The atherosclerosis is stimulated by cardiotrophin-1, fetuin-A, kisspeptin-10, and stanniocalcin (STC)-2-derived segments, but is suppressed by STC-1, omentin-1, tumor necrosis factor-stimulated gene-6 (TSG-6), and urocortin-1. This study also shows that plasma levels of kisspeptin-10, omentin-1, and TSG-6 may become candidates for biomarker of coronary atherosclerosis in patients with ischemic heart disease. Further studies are needed to make anti-atherosclerotic drugs on the basis of the good peptides, such as omentin-1, and TSG-6, and urocortin-1.

Research Products

• [Journal Article] Combination therapy with a sodium-glucose cotransporter 2 inhibitor and a dipeptidyl peptidase-4 inhibitor additively suppresses macrophage foam cell formation and atherosclerosis in diabetic mice (2017)
  • Author(s): Terasaki M, Hiromura M, Mori Y, Kohashi K, Kushima H, Ohara M, Watanabe T, Andersson O, Hirano T
  • Journal Title: Int J Endocrinol Volume: 2017 Pages: 9-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A potent vasoconstrictor kisspeptin-10 induces atherosclerotic plaque progression and instability: reversal by its receptor GPR54 antagonist (2017)
  • Author(s): Sato K, Shirai R, Hontani M, Shinooka R, Hasegawa A, Kichise T, Yamashita T, Yoshizawa H, Watanabe R, Matsuyama T, Ishibashi-Ueda H, Koba S, Kobayashi Y, Hirano T, Watanabe T
  • Journal Title: J Am Heart Assoc Volume: 6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Adipose tissue-derived omentin-1 function and regulation (2017)
  • Author(s): Watanabe T, Watanabe-Kominato K, Takahashi Y, Kojima M, Watanabe R
  • Journal Title: Compr Physiol Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Atheroprotective effects of tumor necrosis factor-stimulated gene-6 (2016)
  • Author(s): Watanabe R, Watanabe H, Takahashi Y, Kojima M, Konii H, Watanabe K, Shirai R, Sato K, Matsuyama T, Ishibashi-Ueda H, Iso Y, Koba S, Kobayashi Y, Hirano T, Watanabe T
  • Journal Title: JACC Basic to Transl Sci Volume: 6 Pages: 494-509
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Suppressive effects of glucose-dependent insulinotropic polypeptide on cardiac hypertrophy and fibrosis in angiotensin II-infused mouse models (2016)
  • Author(s): Hiromura M, Mori Y, Kohashi K, Terasaki M, Shinmura K, Negoro T, Kawashima H, Kogure M, Wachi T, Watanabe R, Sato K, Kushima H, Tomoyasu M, Nakano Y, Yamada Y, Watanabe T, Hirano T
  • Journal Title: Circ J Volume: 80 Pages: 1988-1997
  • NAID: 130005406847
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Counteractive effects of omentin-1 against atherogenesis (2016)
  • Author(s): Watanabe K, Watanabe R, Konii H, Shirai R, Sato K, Matsuyama T, Ishibashi-Ueda H, Koba S, Kobayashi Y, Hirano T, Watanabe T
  • Journal Title: Cardiovasc Res Volume: 110 Issue: 1 Pages: 118-128
  • DOI: 10.1093/cvr/cvw016
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Facilitatory effects of fetuin-A on atherosclerosis (2016)
  • Author(s): Naito C, Hashimoto M, Watanabe K, Shirai R, Takahashi Y, Kojima M, Watanabe R, Sato K, Iso Y, Matsuyama T, Suzuki H, Ishibashi-Ueda H, Watanabe T
  • Journal Title: Atherosclerosis Volume: 246 Pages: 344-351
  • DOI: 10.1016/j.atherosclerosis.2016.01.037
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A Dipeptidyl Peptidase-4 Inhibitor but not Incretins Suppresses Abdominal Aortic Aneurysms in Angiotensin II-Infused Apolipoprotein E-Null Mice (2016)
  • Author(s): Kohashi K, Hiromura M, Mori Y, Terasaki M, Watanabe T, Kushima H, Shinmura K, Tomoyasu M, Nagashima M, Hirano T
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 23 Issue: 4 Pages: 441-454
  • DOI: 10.5551/jat.31997
  • NAID: 130005141423
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Amelioration of hyperglycemia with a sodium-glucose cotransporter 2 inhibitor prevents macrophage-driven atherosclerosis through macrophage foam cell formation suppression in type 1 and type 2 diabetic mice (2015)
  • Author(s): Terasaki M, Hiromura M, Mori Y, Kohashi K, Nagashima M, Kushima H, Watanabe T, Hirano T
  • Journal Title: PLOS ONE Volume: 10 Issue: 11 Pages: e0143396-e0143396
  • DOI: 10.1371/journal.pone.0143396
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transforming growth factor-β signaling enhancement by long-term exposure to hypoxia in a tumor microenvironment composed of Lewis lung carcinoma cells (2015)
  • Author(s): Furuta C, Miyamoto T, Takagi T, Noguchi Y, Kaneko J, Itoh S, Watanabe T, Itoh F
  • Journal Title: Cancer Sci Volume: 106 Issue: 11 Pages: 1524-1533
  • DOI: 10.1111/cas.12773
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structure analysis of GLP-1 in DPC micelle (2015)
  • Author(s): Mori S, Yamada H, Noguchi Y, Miyakawa T, Morikawa R, Watanabe T, Takasu M
  • Journal Title: Pept Sci Volume: Suppl Pages: 213-216
• [Journal Article] Vasoprotective effects of urocortin 1 against atherosclerosis in vitro and in vivo (2014)
  • Author(s): Hasegawa A, Sato K, Shirai R, Watanabe R, Yamamoto K, Watanabe K, Nohtomi K, Hirano T, Watanabe T.
  • Journal Title: PLoS One Volume: 9 Issue: 12 Pages: e110866-e110866
  • DOI: 10.1371/journal.pone.0110866
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Atheroprotective effects of tumor necrosis factor-stimulated gene-6 (2017)
  • Author(s): Watanabe R, Takahashi Y, Kojima M, Shirai R, Sato K, Watanabe T
  • Organizer: 66th Annual Scientific Sessions of the American College of Cardiology
  • Place of Presentation: Walter E. Washington Convention Center, Washington, DC, USA
  • Year and Date: 2017-03-17
  • Int'l Joint Research
• [Presentation] Tumor Necrosis Factor-Stimulated Gene-6 (TSG-6)の動脈硬化抑制作用 (2016)
  • Author(s): 渡部麗奈, 高橋由衣, 小島美穂, 小湊夏帆, 白井玲美奈, 佐藤健吾, 松山高明, 木庭新治, 平野勉, 渡部琢也
  • Organizer: 第20回 日本心血管内分泌代謝学会学術集会
  • Place of Presentation: 東京コンベンションホール、東京都中央区
  • Year and Date: 2016-12-16
• [Presentation] Catestatinの動脈硬化抑制作用 (2016)
  • Author(s): 小島美穂, 渡部麗奈, 小湊夏帆, 高橋由衣, 佐藤健吾, 森雄作, 平野勉, 渡部琢也
  • Organizer: 第20回 日本心血管内分泌代謝学会学術集会
  • Place of Presentation: 東京コンベンションホール、東京都中央区
  • Year and Date: 2016-12-16
• [Presentation] 新規植物ペプチドOsmotinの動脈硬化予防作用 (2016)
  • Author(s): 高橋由衣, 渡部麗奈, 小湊夏帆, 小島美穂, 白井玲美奈, 佐藤健吾, 渡部琢也
  • Organizer: 第20回 日本心血管内分泌代謝学会学術集会
  • Place of Presentation: 東京コンベンションホール、東京都中央区
  • Year and Date: 2016-12-16
• [Presentation] Adropinの動脈硬化抑制作用 (2016)
  • Author(s): 山下智之、白井玲美奈、佐藤健吾、渡部琢也
  • Organizer: 第20回 日本心血管内分泌代謝学会学術集会
  • Place of Presentation: 東京コンベンションホール、東京都中央区
  • Year and Date: 2016-12-16
• [Presentation] Neopterin reacts against vascular inflammatory and atherosclerosis (2016)
  • Author(s): Shirai R, Sato K, Matsuyama T, Koba S, Watanebe R, Watanabe K, Hirano T, Watanabe T
  • Organizer: 38th Congress of the European Society of Cardiology
  • Place of Presentation: Rome, Italy
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] Preventive effects of catestatin on atherosclerosis (2016)
  • Author(s): Kojima M, Watanabe R, Watanabe K, Takahashi Y, Sato K, Mori Y, Hirano T, Watanabe T
  • Organizer: 第48回 日本動脈硬化学会学術集会
  • Place of Presentation: 京王プラザホテル、東京都新宿区
  • Year and Date: 2016-07-14
• [Presentation] Preventive effects of osmotin on atherosclerosis (2016)
  • Author(s): Takahashi Y, Watanabe R, Watanabe K, Kojima M, Shirai R, Sato K, Watanabe T
  • Organizer: 第48回 日本動脈硬化学会学術集会
  • Place of Presentation: 京王プラザホテル、東京都新宿区
  • Year and Date: 2016-07-14
• [Presentation] Preventive effects of chemerin on atherosclerosis (2016)
  • Author(s): Yoshizawa H, Sato K, Shirai R, Yamashita T, Matsuyama T, Koba S, Hirano T, Watanabe T
  • Organizer: 第48回 日本動脈硬化学会学術集会
  • Place of Presentation: 京王プラザホテル、東京都新宿区
  • Year and Date: 2016-07-14
• [Presentation] Suppressive effects of glucose-dependent insulinotropic polypeptide on cardiac hypertrophy and fibrosis in angiotensin II-infused mouse models (2016)
  • Author(s): Hiromura M, Mori Y, Kohashi K, Terasaki M, Shinmura K, Kushima H, Tomoyasu M, Yamada Y, Watanabe T, Hirano T
  • Organizer: 76th Scientific Sessions of American Diabetes Association
  • Place of Presentation: New Orleans, Louisiana, USA
  • Year and Date: 2016-06-10
  • Int'l Joint Research
• [Presentation] Stimulatory effects of fetuin-A on atherosclerosis (2016)
  • Author(s): Watanabe T, Watanabe R, Takahashi Y, Kojima M, Watanabe K, Shirai R, Sato K, Iso Y, Matsuyama T
  • Organizer: 65th Annual Scientific Sessions of the American College of Cardiology
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 2016-04-02
  • Int'l Joint Research
• [Presentation] Counteractive effects of neopterin on atherosclerosis (2016)
  • Author(s): Shirai R, Sato K, Matsuyama T, Koba S, Watanabe R, Watanabe K, Watanabe T
  • Organizer: 65th Annual Scientific Sessions of the American College of Cardiology
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 2016-04-02
  • Int'l Joint Research
• [Presentation] A potent vasoconstrictor kisspeptin-10 accelerates atherosclerotic plaque progression and instability (2016)
  • Author(s): Sato K, Shirai R, Yamashita T, Yoshizawa H, Matsuyama T, Koba S, Watanabe T
  • Organizer: 65th Annual Scientific Sessions of the American College of Cardiology
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 2016-04-02
  • Int'l Joint Research
• [Presentation] 血管炎症および動脈硬化に対するNeopterinの抑制作用 (2016)
  • Author(s): 白井玲美奈、渡部琢也
  • Organizer: 第23回 動脈硬化若手研究会
  • Place of Presentation: 第一三共本社ビル、東京都中央区
• [Presentation] Kisspeptin-10 (KP10)は動脈硬化性プラークの進展および不安定化を促進する (2015)
  • Author(s): 佐藤健吾、白井玲美奈、松山高明、木庭新治、渡部琢也
  • Organizer: 第19回 日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-10
• [Presentation] Neopterinの抗炎症・抗動脈硬化作用 (2015)
  • Author(s): 白井玲美奈、佐藤健吾、松山高明、木庭新治、渡部琢也
  • Organizer: 第19回 日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-10
• [Presentation] Counteractive effects of omentin-1 against atherogenesis (2015)
  • Author(s): Watanabe K, Watanabe R, Konii H, Shirai R, Sato K, Matsuyama T, Ishibashi-Ueda H, Koba S, Kobayashi Y, Hirano T, Watanabe T
  • Organizer: American Heart Association Scientific Sessions 2015
  • Place of Presentation: Orland, Florida, USA
  • Year and Date: 2015-11-13
  • Int'l Joint Research
• [Presentation] Preventive effects of neopterin on atherosclerosis (2015)
  • Author(s): Shirai R, Sato K, Watanabe K, Watanabe R, Matsuyama T, Koba S, Hirano T, Watanabe T
  • Organizer: American Heart Association Scientific Sessions 2015
  • Place of Presentation: Orland, Florida, USA
  • Year and Date: 2015-11-13
  • Int'l Joint Research
• [Presentation] A potent vasoconstrictor kisspeptin-10 induces atherosclerotic plaque progression and instability (2015)
  • Author(s): Shirai R, Sato K, Matsuyama T, Koba S, Hirano T, Watanabe T
  • Organizer: American Heart Association Scientific Sessions 2015
  • Place of Presentation: Orland, Florida, USA
  • Year and Date: 2015-11-13
  • Int'l Joint Research
• [Presentation] GLP-1の構造変化に関する分子動力学シミュレーション (2015)
  • Author(s): 森咲季子、山田寛尚、野口瑶、宮川毅、森河良太、渡部琢也、高須昌子
  • Organizer: 日本物理学会 2015年秋季大会
  • Place of Presentation: 大阪
  • Year and Date: 2015-09-16
• [Presentation] Preventive effects of omentin-1 on atherosclerosis (2015)
  • Author(s): Watanabe K, Watanabe R, Konii H, Shirai R, Sato K, Matsuyama T, Koba S, Hirano T, Watanabe T
  • Organizer: 第47回 日本動脈硬化学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2015-07-09
• [Presentation] Suppresive effects of neopterin on atherosclerosis (2015)
  • Author(s): Shirai R, Sato K, Watanabe K, Watanabe R, Hirano T, Watanabe T
  • Organizer: 第47回 日本動脈硬化学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2015-07-09
• [Presentation] NeopterinのIn Vitroにおける動脈硬化に対する作用 (2014)
  • Author(s): 白井玲美奈、佐藤健吾、渡部琢也
  • Organizer: 第18回 日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-21 – 2014-11-22
• [Presentation] Preventive effects of tumor necrosis factor-stimulated gene-6 on atherosclerosis (2014)
  • Author(s): Rena Watanabe, Kaho Watanabe, Remina Shirai, Hanae Konii, Kengo Sato, Takuya Watanabe
  • Organizer: American Heart Association Scientific Sessions 2014
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 2014-11-16 – 2014-11-19
• [Presentation] Tumor Necrosis Factor-Stimulated Gene-6 (TSG-6) の抗動脈硬化作用 (2014)
  • Author(s): 佐藤健吾、渡部麗奈、渡部琢也
  • Organizer: 第21回 動脈硬化若手研究会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-25
• [Presentation] Preventive effects of tumor necrosis factor-stimulated gene-6 on atherosclerosis (2014)
  • Author(s): 渡部麗奈、佐藤健吾、渡部仁美、兒仁井花恵、 長谷川晶紀、山本圭吾、渡部琢也
  • Organizer: 第46回 日本動脈硬化学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-10 – 2014-07-11