Elucidation of ectopic expression of fatty acid-binding protein 4 in endovascular injury and application to clinical therapies

• Project/Area Number: 17K09594
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Sapporo Medical University
• Principal Investigator: Furuhashi Masato 札幌医科大学, 医学部, 講師 (20563852)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 脂肪酸結合タンパク / 血管内皮細胞 / 血管傷害 / 新生内膜形成 / 炎症 / 脂肪組織 / 循環器・高血圧 / 脂質

Outline of Final Research Achievements

Fatty acid-binding protein 4 (FABP4) is expressed in adipocytes and macrophages and plays significant roles in the development of insulin resistance and atherosclerosis. The present study demonstrated that FABP4 was ectopically induced in endothelial cells by cellular senescence and vascular injury. Furthermore, secreted FABP4 from injured vascular endothelial cells promoted inflammatory response in several cells, proliferation and migration in vascular smooth muscle cells, and endothelial dysfunction in vascular endothelial cells, leading to the development of neointima formation after vascular injury.

Academic Significance and Societal Importance of the Research Achievements

血管内皮傷害時における異所性発現型FABP4の発現機構と局所分泌されるFABP4の作用の包括的な解明により、血管炎や冠動脈インターベンションなどで問題となる再狭窄予防に対する新規治療法に応用できる可能性がある。

Research Products

• [Journal Article] Differential regulation of hypoxanthine and xanthine by obesity in a general population (2020)
  • Author(s): Furuhashi Masato、Koyama Masayuki、Higashiura Yukimura、Murase Takayo、Nakamura Takashi、Matsumoto Megumi、Sakai Akiko、Ohnishi Hirofumi、Tanaka Marenao、Saitoh Shigeyuki、Moniwa Norihito、Shimamoto Kazuaki、Miura Tetsuji
  • Journal Title: Journal of Diabetes Investigation Volume: - Issue: 4 Pages: 878-887
  • DOI: 10.1111/jdi.13207
  • Peer Reviewed / Open Access
• [Journal Article] Fatty Acid-Binding Protein 4 in Cardiovascular and Metabolic Diseases (2019)
  • Author(s): Furuhashi M.
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 26 Issue: 3 Pages: 216-232
  • DOI: 10.5551/jat.48710
  • NAID: 130007605961
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2019-03-01
  • Peer Reviewed / Open Access
• [Journal Article] Differential Phenotypes in Perivascular Adipose Tissue Surrounding the Internal Thoracic Artery and Diseased Coronary Artery. (2019)
  • Author(s): Numaguchi R, Furuhashi M, Matsumoto M, Sato H, Yanase Y, Kuroda Y, Harada R, Ito T, Higashiura Y, Koyama M, Tanaka M, Moniwa N, Nakamura M, Doi H, Miura T, Kawaharada N.
  • Journal Title: J Am Heart Assoc Volume: 8 Issue: 2 Pages: 216-232
  • DOI: 10.1161/jaha.118.011147
  • Peer Reviewed / Open Access
• [Journal Article] Annual change in plasma xanthine oxidoreductase activity is associated with changes in liver enzymes and body weight (2019)
  • Author(s): Furuhashi Masato、Koyama Masayuki、Matsumoto Megumi、Murase Takayo、Nakamura Takashi、Higashiura Yukimura、Tanaka Marenao、Moniwa Norihito、Ohnishi Hirofumi、Saitoh Shigeyuki、Shimamoto Kazuaki、Miura Tetsuji
  • Journal Title: Endocrine Journal Volume: 66 Issue: 9 Pages: 777-786
  • DOI: 10.1507/endocrj.EJ19-0053
  • NAID: 130007719399
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] 動脈硬化の新たな治療ターゲットとしての脂肪酸結合蛋白 (2019)
  • Author(s): 古橋眞人
  • Journal Title: 医学のあゆみ Volume: 68 Pages: 349-354
• [Journal Article] Plasma Xanthine Oxidoreductase Activity as a Novel Biomarker of Metabolic Disorders in a General Population (2018)
  • Author(s): Furuhashi M, Matsumoto M, Tanaka M, Moniwa N, Murase T, Nakamura T, Ohnishi H, Saitoh S, Shimamoto K, Miura T.
  • Journal Title: Circulation Journal Volume: 82 Issue: 7 Pages: 1892-1899
  • DOI: 10.1253/circj.CJ-18-0082
  • NAID: 130007410626
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2018-06-25
  • Peer Reviewed / Open Access
• [Journal Article] Independent links between plasma xanthine oxidoreductase activity and levels of adipokines. (2018)
  • Author(s): Furuhashi M, Matsumoto M, Murase T, Nakamura T, Higashiura Y, Koyama M, Tanaka M, Moniwa N, Ohnishi H, Saitoh S, Shimamoto K, Miura T.
  • Journal Title: J Diabetes Investig Volume: 印刷中 Issue: 4 Pages: 1059-1067
  • DOI: 10.1111/jdi.12982
  • Peer Reviewed / Open Access
• [Journal Article] Circulating Fatty Acid-Binding Protein 4 Concentration Predicts the Progression of Carotid Atherosclerosis in a General Population Without Medication (2018)
  • Author(s): Masato Furuhashi, Satoshi Yuda, Atsuko Muranaka, Mina Kawamukai, Megumi Matsumoto, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura
  • Journal Title: Circulation Journal Volume: 82 Issue: 4 Pages: 1121-1129
  • DOI: 10.1253/circj.CJ-17-1295
  • NAID: 130006528585
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] Unexpected high plasma xanthine oxidoreductase activity in female subjects with low levels of uric acid (2018)
  • Author(s): Furuhashi M, Mori K, Tanaka M, Maeda T, Matsumoto M, Murase T, Nakamura T, Koyama M, Moniwa N, Ohnishi H, Saitoh S, Shimamoto K, Miura T.
  • Journal Title: Endocrine Journal Volume: 65 Issue: 11 Pages: 1083-1092
  • DOI: 10.1507/endocrj.EJ18-0127
  • NAID: 130007537274
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Accuracy of flash glucose monitoring in insulin-treated patients with type 2 diabetes. (2018)
  • Author(s): Sato T, Oshima H, Nakata K, Kimura Y, Yano T, Furuhashi M, Tanno M, Miki T, Miura T.
  • Journal Title: J Diabetes Investig Volume: 印刷中 Issue: 3 Pages: 846-850
  • DOI: 10.1111/jdi.12954
  • Peer Reviewed / Open Access
• [Journal Article] PCSK9阻害薬の効果が不安定になった症例 (2018)
  • Author(s): 古橋眞人
  • Journal Title: News and Scope (日本動脈硬化学会) Volume: 1
• [Journal Article] CKDの新規治療ターゲットとしての異所性FABP4発現の可能性 (2018)
  • Author(s): 古橋眞人, 東浦幸村, 田中希尚
  • Journal Title: 血圧 Volume: 25 Pages: 630-635
• [Journal Article] 心血管合併症予防と上流を意識した糖尿病治療：新規治療ターゲットとしての脂肪酸結合蛋白4の可能性 (2018)
  • Author(s): 古橋眞人, 東浦幸村
  • Journal Title: 血圧 Volume: 25 Pages: 844-849
• [Journal Article] Serum FABP5 concentration is a potential biomarker for residual risk of atherosclerosis in relation to cholesterol efflux from macrophages. (2017)
  • Author(s): Furuhashi M, Ogura M, Matsumoto M, Yuda S, Muranaka A, Kawamukai M, Omori A, Tanaka M, Moniwa N, Ohnishi H, Saitoh S, Harada-Shiba M, Shimamoto K, Miura T.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 217-217
  • DOI: 10.1038/s41598-017-00177-w
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ectopic Fatty Acid-Binding Protein 4 Expression in the Vascular Endothelium is Involved in Neointima Formation After Vascular Injury (2017)
  • Author(s): Fuseya Takahiro, Furuhashi Masato, Matsumoto Megumi, Watanabe Yuki, Hoshina Kyoko, Mita Tomohiro, Ishimura Shutaro, Tanaka Marenao, Miura Tetsuji
  • Journal Title: J Am Heart Assoc Volume: 6 Issue: 9
  • DOI: 10.1161/jaha.117.006377
  • Peer Reviewed / Open Access
• [Journal Article] Impact of the Number of Anti-Thrombosis Agents in Hemodialysis Patients: BOREAS-HD2 Study (2017)
  • Author(s): Tanaka Marenao、Moniwa Norihito、Ohnishi Hirofumi、Yamashita Tomohisa、Koyama Masayuki、Gocho Yufu、Nishizawa Keitaro、Kimura Yukishige、Sugawara Hirohito、Murakami Sayaka、Okazaki Yusuke、Furuhashi Masato、Yoshida Hideaki、Miura Tetsuji
  • Journal Title: Kidney Blood Press Res Volume: 42 Issue: 3 Pages: 553-564
  • DOI: 10.1159/000480487
  • Peer Reviewed / Open Access
• [Journal Article] A Case of Crescentic Glomerulonephritis Complicated with Hypocomplementemic Urticarial Vasculitis Syndrome and ANCA-Associated Vasculitis (2017)
  • Author(s): Tanaka Marenao、Moniwa Norihito、Mita Tomohiro、Tobisawa Toshiyuki、Matsumoto Tamaki、Mochizuki Atsushi、Yamashita Tomohisa、Yano Toshiyuki、Furuhashi Masato、Miura Tetsuji
  • Journal Title: Case Rep Nephrol Dial Volume: 7 Issue: 3 Pages: 144-153
  • DOI: 10.1159/000484476
  • Peer Reviewed / Open Access
• [Journal Article] 代謝および高血圧関連疾患における脂肪酸結合蛋白4 (2017)
  • Author(s): 古橋眞人
  • Journal Title: 医学のあゆみ Volume: 261 Pages: 818-823
• [Presentation] Protection Against Metaflammation in Perivascular Adipose Tissue Surrounding the Internal Thoracic Artery, A Vessel Resistant to Atherosclerosis. (2019)
  • Author(s): Furuhashi M, Numaguchi R, Matsumoto M, Kawaharada N, Miura T.
  • Organizer: American Heart Association Vascular Discovery: From Genes to Medicine
  • Int'l Joint Research
• [Presentation] キサンチン酸化還元酵素 (XOR) 活性と各種アディポカインとの関連 (2019)
  • Author(s): 古橋眞人、松本めぐみ、東浦幸村、小山雅之、田中希尚、茂庭仁人、村瀬貴代、中村敬志、大西浩文、斎藤重幸、島本和明、三浦哲嗣
  • Organizer: 第52回日本痛風・核酸代謝学会総会
• [Presentation] Symposium “Novel Therapeutic Targets for Atherosclerosis”. Fatty Acid-Binding Proteins, FABP4 and FABP5, as Residual Risk of Atherosclerosis. (2019)
  • Author(s): Furuhashi M.
  • Organizer: 第83回日本循環器学会学術集会
  • Invited
• [Presentation] Differential Phenotypes in Perivascular Adipose Tissue Surrounding the Coronary Artery and Internal Thoracic Artery. (2019)
  • Author(s): Numaguchi R, Furuhashi M, Matsumoto M, Harada R, Ito T, Higashiura Y, Tanaka M, Doi H, Miura T, Kawaharada N.
  • Organizer: 第83回日本循環器学会学術集会
• [Presentation] 一般住民におけるキサンチン酸化還元酵素 (XOR) 活性と高血圧との関連 (2019)
  • Author(s): 東浦幸村、古橋眞人、小山雅之、田中希尚、茂庭仁人、松本めぐみ、酒井晶子、村瀬貴代、中村敬志、大西浩文、斎藤重幸、島本和明、三浦哲嗣
  • Organizer: 第42回日本高血圧学会総会
• [Presentation] 一般住民において血漿ピポキサンチン濃度は肥満度および喫煙と関連する (2019)
  • Author(s): 東浦幸村, 古橋眞人, 松本めぐみ, 酒井晶子, 小山雅之, 村瀬貴代, 中村敬志, 田中希尚, 茂庭仁人, 大西浩文, 斎藤重幸, 三浦哲嗣
  • Organizer: 第40回日本肥満学会
• [Presentation] Ectopic Expression of Fatty Acid-Binding Protein 4 in the Vascular Endothelium is Involved in Neointima Formation After Vascular Injury (2018)
  • Author(s): Furuhashi M, Fuseya T, Mita T, Ishimura S, Tanaka M, Miura T.
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] 生活習慣病における血漿キサンチン酸化還元酵素(XOR)活性の意義 (2018)
  • Author(s): 古橋眞人、松本めぐみ、大西浩文、斎藤重幸、村瀬貴代、中村敬志、三浦哲嗣
  • Organizer: 第91回日本内分泌学会学術総会
• [Presentation] 脂肪酸結合タンパク4 (FABP4) 濃度は動脈硬化進展度の予測因子である (2018)
  • Author(s): 古橋眞人、湯田 聡、村中敦子、川向美奈、松本めぐみ、田中希尚、茂庭仁人、大西浩文、斎藤重幸、三浦哲嗣
  • Organizer: 第61回日本糖尿病学会年次学術集会
• [Presentation] 一般住民における尿酸低値例での血漿キサンチン酸化還元酵素(XOR)活性の検討 (2018)
  • Author(s): 森 和真、古橋眞人、田中希尚、村瀬貴代、中村敬志、前田卓人、大西浩文、三浦哲嗣
  • Organizer: 第61回日本腎臓学会学術総会
• [Presentation] 腎疾患症例における尿FABP4排泄量の臨床的意義：腎生検例を用いた検討 (2018)
  • Author(s): 田中希尚、古橋眞人、松本めぐみ、山下智久、茂庭仁人、後町結、前田卓人、滝沢英毅、三浦哲嗣
  • Organizer: 第61回日本腎臓学会学術総会
• [Presentation] 五島雄一郎賞受賞講演: 動脈硬化関連疾患における脂質シャペロンの役割解明 (2018)
  • Author(s): 古橋眞人、松本めぐみ、平光伸也、田中希尚、茂庭仁人、石井潤一、三浦哲嗣
  • Organizer: 第50回日本動脈硬化学会総会学術集会
  • Invited
• [Presentation] 動脈硬化とその関連疾患における新規治療ターゲットとしての脂肪酸結合タンパク (2018)
  • Author(s): 古橋眞人、三浦哲嗣.
  • Organizer: 第50回日本動脈硬化学会総会学術集会
  • Invited
• [Presentation] Ectopic Expression of FABP4 in the Vascular Endothelium is Involved in Neointima Formation After Vascular Injury. (2018)
  • Author(s): Furuhashi M, Fuseya T, Mita T, Ishimura S, Tanaka M, Miura T.
  • Organizer: 第66回日本心臓病学会学術集会
• [Presentation] キサンチン酸化還元酵素 (XOR) 活性とアディポカインとの関連 (2018)
  • Author(s): 東浦幸村、古橋眞人、松本めぐみ、小山雅之、田中希尚、茂庭仁人、村瀬貴代、中村敬志、大西浩文、斎藤重幸、島本和明、三浦哲嗣
  • Organizer: 第41回日本高血圧学会総会
• [Presentation] 脂肪酸結合タンパク4 (FABP4) と心血管・代謝疾患 (2018)
  • Author(s): 古橋眞人、斎藤重幸、三浦哲嗣
  • Organizer: 第91回日本生化学会大会
  • Invited
• [Presentation] 冠動脈疾患患者の内胸動脈周囲脂肪の特徴：冠動脈周囲脂肪との炎症マーカーの比較 (2018)
  • Author(s): 沼口亮介、古橋眞人、松本めぐみ、原田 亮、伊藤寿朗、道井洋吏、川原田修義、三浦哲嗣
  • Organizer: 第39回日本肥満学会
• [Presentation] 冠動脈疾患患者における冠動脈および内胸動脈周囲脂肪組織の性状の違いに関する検討 (2018)
  • Author(s): 沼口亮介、古橋眞人、松本めぐみ、大川陽史、佐藤 宏、安田尚美、柳清洋佑、黒田陽介、原田亮、伊藤寿朗、道井洋吏、三浦哲嗣、川原田修義
  • Organizer: 第59回日本脈管学会総会
• [Presentation] Fatty acid-binding protein 5 as a residual risk for atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia. (2017)
  • Author(s): Ogura M, Furuhashi M, Morimoto M, Matsumoto M, Miura T, Harada-Shiba M.
  • Organizer: The 85th European Atherosclerosis Society Congress
  • Int'l Joint Research
• [Presentation] Ectopic FABP4 expression in the vascular endothelium is involved in neointima formation after vascular injury. (2017)
  • Author(s): Furuhashi M, Fuseya T, Matsumoto M, Mita T, Ishimura S, Tanaka M, Moniwa N, Miura T.
  • Organizer: European Society of Cardiology Congress 2017
  • Int'l Joint Research
• [Presentation] Circulating FABP4 Concentration Predicts the Progression of Carotid Atherosclerosis in a General Population Without Medication. (2017)
  • Author(s): Furuhashi M, Yuda S, Muranaka A, Kawamukai M, Matsumoto M, Tanaka M, Moniwa N, Ohnishi H, Saitoh S, Shimamoto K, Miura T.
  • Organizer: American Heart Association. 2017
  • Int'l Joint Research
• [Presentation] Serum FABP5 is a Potential Biomarker for Residual Risk of Atherosclerosis in Relation to Cholesterol Efflux from Macrophages (2017)
  • Author(s): Furuhashi M, Ogura M, Matsumoto M, Yuda S, Muranaka A, Kawamukai M, Tanaka M, Moniwa N, Ohnishi H, Saitoh S, Harada-Shiba M, Shimamoto K, Miura T.
  • Organizer: 第81回日本循環器学会
• [Presentation] ヒト脂肪組織由来幹細胞における外因性脂肪酸結合タンパク4/5の影響：トランスクリプトームおよびメタボローム解析から (2017)
  • Author(s): 古橋眞人、山本徳則、松本めぐみ、後藤百万、三浦哲嗣
  • Organizer: 第90回日本内分泌学会
• [Presentation] SGLT2阻害薬カナグリフロジン投与による脂肪酸結合タンパク4 (FABP4)濃度の経時的変化とその規定因子の検討 (2017)
  • Author(s): 古橋眞人、松本めぐみ、平光伸也、田中希尚、茂庭仁人、石井潤一、三浦哲嗣
  • Organizer: 第60回日本糖尿病学会
• [Presentation] Serum FABP4 concentration is independently associated with atherosclerosis in a general population without medication. (2017)
  • Author(s): Furuhashi M, Yuda S, Muranaka A, Kawamukai M, Matsumoto M, Tanaka M, Moniwa N, Ohnishi H, Saitoh S, Shimamoto K, Miura T
  • Organizer: 第49回日本動脈硬化学会
• [Presentation] 動脈硬化および脂質異常症治療における新規治療ターゲットとしての脂肪酸結合タンパク4/5 (FABP4/5) (2017)
  • Author(s): 古橋眞人、三浦哲嗣
  • Organizer: 第65回日本心臓病学会
  • Invited
• [Presentation] 心血管・代謝疾患と脂肪酸結合タンパク (2017)
  • Author(s): 古橋眞人、三浦哲嗣
  • Organizer: 第38回日本肥満学会
  • Invited
• [Presentation] 心血管合併症予防と上流を意識した糖尿病治療 (2017)
  • Author(s): 古橋眞人、斎藤重幸、三浦哲嗣
  • Organizer: 第40回日本高血圧学会
  • Invited
• [Presentation] 生活習慣病の新規バイオマーカーとしてのキサンチン酸化還元酵素(XOR)活性 (2017)
  • Author(s): 古橋眞人、三浦哲嗣
  • Organizer: 第40回日本高血圧学会
  • Invited
• [Presentation] 慢性腎臓病の新規治療ターゲットとしての異所性FABP4発現の可能性 (2017)
  • Author(s): 古橋眞人、田中希尚、三浦哲嗣
  • Organizer: 第40回日本高血圧学会
  • Invited
• [Book] 動脈硬化UPDATE (2019)
  • Author(s): 古橋眞人
  • Publisher: 医歯薬出版株式会社
• [Book] Biogenesis of Fatty Acids, Lipids and Membranes, Handbook of Hydrocarbon and Lipid Microbiology: Fatty acid-binding proteins, a family of lipid chaperones. (2017)
  • Author(s): Furuhashi M
  • Total Pages: 16
  • Publisher: Springer
• [Remarks] 心血管・腎・代謝疾患における脂肪酸結合タンパク4 (FABP4)の役割解明
  • URL: http://web.sapmed.ac.jp/kikaku/degitalbook/research_seeds/FLASH/index.html