The role of ADAMTS in cardiovascular disease

• Project/Area Number: 25461110
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Okayama University
• Principal Investigator: KUSACHI Shozo 岡山大学, 保健学研究科, 特命教授 (30214943)
• Co-Investigator(Kenkyū-buntansha): HIROHATA Satoshi 岡山大学, 大学院保健学研究科, 教授 (90332791) ; OGAWA Hiroko 岡山大学, 大学病院, 助教 (70423283)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 心臓病学 / ＥＣＭ / 細胞外マトリックス

Outline of Final Research Achievements

The aim of this study was to examine the role of ADAMTS in cardiovascular disease. We used ADAMTS knockout mouse in this study. First, we produced ADAMTS4/ADAMTS5 double knockout mouse. Because ADAMTS4 (aggrecanase-1) and ADAMTS5 (aggrecanase-2) share the substrates, one of these two molecule may compensate the biological function in a single knockout mouse, we decided to produce double knockout mouse.
The double knockout mice were survived and there was no dwarfism observed. There was no particular abnormality in the tissue development. We then cross double knockout mice with ApoE knockout mouse. ApoE knockout mouse is used for atherosclerosis study. We succeeded to produced triple knockout mice and we gave them high-fat diet. It was interesting that there was a significant difference in the development of atherosclerosis between ApoE single and triple knockout mice.

Research Products

• [Journal Article] Subclavian steal syndrome: a case report and review of advances in diagnostic and treatment approaches. (2016)
  • Author(s): Komatsubara I, Kondo J, Akiyama M, Takeuchi H, Nogami K, Usui S, Hirohata S, Kusachi S
  • Journal Title: Cardiovasc Revasc Med Volume: 17(1) Issue: 1 Pages: 54-58
  • DOI: 10.1016/j.carrev.2015.11.001
  • Peer Reviewed
• [Journal Article] MMP-13 is constitutively produced in human chondrocytes and co-endocytosed with ADAMTS-5 and TIMP-3 by the endocytic receptor LRP1 (2016)
  • Author(s): Yamamoto K, Okano H, Miyagawa W, Visse R, Shitomi Y, Santamaria S, Dudhia J, Troeberg L, Strickland DK, Hirohata S, Nagase H
  • Journal Title: Matrix Biol Volume: S0945-053X(16) Pages: 30031-30032
  • DOI: 10.1016/j.matbio.2016.03.007
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Interleukin-1β induced nuclear factor-κB binds to a disintegrin-like and metalloproteinase with thrombospondin type 1 motif 9 promoter in human chondrosarcoma cells. (2015)
  • Author(s): Altuntas A, Halacli SO, Cakmak O, Erden G, Akyol S, Ugurcu V, Hirohata S, Demircan K.
  • Journal Title: Mol Med Rep. Volume: in press Issue: 1 Pages: 595-600
  • DOI: 10.3892/mmr.2015.3444
  • Peer Reviewed
• [Journal Article] Eosinophil Cationic Protein Shows Survival Effect on H9c2 Cardiac Myoblast Cells with Enhanced Phosphorylation of ERK and Akt/GSK-3β under Oxidative Stress. (2015)
  • Author(s): Ishii H, Kamikawa S, Hirohata S, Mizutani A, Abe K, Seno M, Oohashi T, Ninomiya Y
  • Journal Title: Acta Med Okayama. Volume: 69(3) Pages: 145-153
  • NAID: 120005621908
  • Peer Reviewed
• [Journal Article] ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor (2014)
  • Author(s): Inagaki J, Takahashi K, Ogawa H, Asano K, Faruk Hatipoglu O, Cilek MZ, Obika M, Ohtsuki T, Hofmann M, Kusachi S, Ninomiya Y, Hirohata S
  • Journal Title: Exp Cell Res Volume: 323(2) Issue: 2 Pages: 263-75
  • DOI: 10.1016/j.yexcr.2014.03.002
  • Peer Reviewed / Open Access
• [Journal Article] Olmesartan reduces inflammatory biomarkers in patients with stable coronary artery disease undergoing percutaneous coronary intervention: results from the OLIVUS trial. (2014)
  • Author(s): Miyoshi T, Hirohata A, Usui S, Yamamoto K, Murakami T, Komatsubara I, Kusachi S, Ohe T, Nakamura K, Ito H.
  • Journal Title: Heart Vessels. Volume: 29(2) Issue: 2 Pages: 178-185
  • DOI: 10.1007/s00380-013-0343-0
  • Peer Reviewed
• [Journal Article] Usefulness of dabigatran etexilate as periprocedural anticoagulation therapy for atrial fibrillation ablation. (2013)
  • Author(s): Yamaji H, Murakami T, Hina K, Higashiya S, Kawamura H, Murakami M, Kamikawa S, Hirohata S, Kusachi S.
  • Journal Title: Clin Drug Investig. Volume: 33（6） Issue: 6 Pages: 409-418
  • DOI: 10.1007/s40261-013-0081-1
  • Peer Reviewed
• [Journal Article] Reduced Diurnal Variation of Heart Rate is Associated With Increased Plasma B-Type Natriuretic Peptide Level in Patients With Atrial Fibrillation. (2013)
  • Author(s): Kamikawa S, Miyoshi T, Doi M, Orita N, Sangawa M, Nakatsu T, Noguchi Y, Hirohata S, Kusachi S, Nakamura K, Ito H
  • Journal Title: Clin Cardiol. Volume: 36(7) Issue: 7 Pages: 394-400
  • DOI: 10.1002/clc.22128
  • Peer Reviewed
• [Journal Article] Adaptive-servo ventilation combined with deep sedation is an effective strategy during pulmonary vein isolation (2013)
  • Author(s): Murakami T, Yamaji H, Numa K, Kawamura H, Murakami M, Higashiya S, Kamikawa S, Hina K, Hirohata S, Kusachi S
  • Journal Title: Europace Volume: 15(7) Issue: 7 Pages: 951-956
  • DOI: 10.1093/europace/eut007
  • Peer Reviewed
• [Journal Article] Serum adipocyte fatty acid-binding protein is independently associated with complex coronary lesions in patients with stable coronary artery disease (2013)
  • Author(s): Kajiya M, Miyoshi T, Doi M, Usui S, Iwamoto M, Takeda K, Nosaka K, Nakayama R, Hirohata S, Kusachi S, Nakamura K, Ito H
  • Journal Title: Heart Vessels Volume: 28(6) Issue: 6 Pages: 696-703
  • DOI: 10.1007/s00380-012-0310-1
  • Peer Reviewed
• [Presentation] Distribution of versican and its degradation by ADAMTS protease in the tumor microenvironment (2016)
  • Author(s): Satoshi Hirohata, Keiichi Asano, Junko Inagaki, Takashi Ohtsuki, Nao Yamanokuchi, Shogo Watanabe, Toshitaka Oohashi
  • Organizer: KSBMB International Conference 2016
  • Place of Presentation: ソウル
  • Year and Date: 2016-05-18
  • Int'l Joint Research / Invited
• [Presentation] The diverse function of a disintegrin and metalloproteinase with thrombospondin motif-1 (ADAMTS1) (2016)
  • Author(s): Satoshi Hirohata
  • Organizer: TIDRC International Symposium -Inflammation and Tumor microenvironment-
  • Place of Presentation: ソウル
  • Year and Date: 2016-05-17
  • Int'l Joint Research / Invited
• [Presentation] ADAMTS1 null mice demonstrated omphalocele phenotype. (2015)
  • Author(s): Satoshi Hirohata, Omer Faruk Hatipoglu, Eriko Kusunoki, Takashi Ohtsuki, Junko Inagaki, Shozo Kusachi, Yoshifumi Ninomiya
  • Organizer: ゴードンカンファレンス matrix metalloproteinase
  • Place of Presentation: 米国 メイン州
  • Year and Date: 2015-08-02
  • Int'l Joint Research
• [Presentation] 低酸素運動負荷時の血圧応答と家庭血圧の関連 (2014)
  • Author(s): 豊永慎二、間島圭一、中津高明、廣畑 聡、草地省藏
  • Organizer: 第37回日本高血圧学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor. (2014)
  • Author(s): Junko Inagaki, Katsuyuki Takahashi, Hiroko Ogawa, Omer Hatipoglu, Mehmet Cilek, Masanari Obika, Takashi Ohtsuki, Shozo Kusachi, Yoshifumi Ninomiya, Satoshi Hirohata
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: 京都市
  • Year and Date: 2014-04-14 – 2014-04-17
• [Presentation] Red Cell Distribution Width Is an Important Factor for Evaluatiin of Diastolic Dysfunction in Chronic Hemodialysis Patients (2014)
  • Author(s): Hirofumi Kumashiro, Satoshi Hirohata, Asami Yamanishi, Chiho Tomioka, Shozo Kusachi
  • Organizer: 第78回日本循環器学会総会
  • Place of Presentation: 東京
• [Presentation] ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor (2014)
  • Author(s): Junko Inagaki, Katsuyuki Takahashi, Hiroko Ogawa, Omer Hatipoglu, Mehmet Cilek, Masanari Obika, Takashi Ohtsuki, Shozo Kusachi, Yoshifumi Ninomiya, Satoshi Hirohata
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: 京都
• [Presentation] Red cell distribution width is an effective tool for detecting diastolic dysfunction in chronic hemodialysis patients (2013)
  • Author(s): Hirofumi Kumashiro, Satoshi Hirohata, Asami Yamanishi, Chiho Tomioka, Shozo Kusachi
  • Organizer: 欧州心不全会議 2013
  • Place of Presentation: リスボン（ポルトガル）