Consideration of the strategy for prevention of cardiovascular disease from the perspective of fatty acid composition and catalytic enzyme.

• Project/Area Number: 23790656
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hygiene
• Research Institution: Gunma University
• Principal Investigator: MATSUI HIROKI 群馬大学, 保健学研究科, 助教 (20431710)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 心血管病 / 遊離脂肪酸 / メタボリックシンドローム / 予防医学 / 触媒酵素 / 脂肪酸分画 / 糖尿病 / 内臓肥満 / 心筋傷害 / 動脈硬化 / 飽和脂肪酸 / 不飽和脂肪酸 / 脂肪酸触媒酵素

Research Abstract

The clinical findings suggest that elevated plasma free fatty acids could be associated with acceleration of cardiovascular disease. However, little is known about the mechanism by which disturbance for the effect of fatty acid composition in heart or vessel results in cardiovascular diseases. We have focused on two fatty acid catalytic enzymes, Stearoyl-CoA desaturase 1 (SCD1), that catalyzes the synthesis of monounsaturated fatty acids (MUFA) from saturated fatty acids (SFA), Elongase of long chain fatty acids 6 (Elovl6), that catalyzes the elongation of long-chain SFA and MUFA. Collectively, our results suggest that perturbation of fatty acid composition in heart and blood vessel leads to the onset and development of cardiovascular disease, and also suggest that SCD1 and Elovl6 as the novel protective and therapeutic target for cardiovascular disease.

Research Products

• [Journal Article] Fatty Acid Binding Protein 4 and 5 Play a Crucial Role in Thermogenesis under the Conditions of Fasting and Cold Stress (2014)
  • Author(s): Syamsunarno MR, Matsui H, 他12名
  • Journal Title: PLoS ONE Volume: 9(3) Issue: 3 Pages: 90825-90825
  • DOI: 10.1371/journal.pone.0090825
  • Peer Reviewed / Open Access
• [Journal Article] A critical role of fatty acid binding protein 4 and 5 (FABP4/5) in the systemic response to fasting (2013)
  • Author(s): Syamsunarno MR, Iso T, Hanaoka H, Yamaguchi A, Obokata M, Koitabashi N, Goto K, Hishiki T, Nagahata Y, Matsui H, Sano M, Kobayashi M, Kikuchi O, Sasaki T, Maeda K, Murakami M, Kitamura T, Suematsu M, Tsushima Y, Endo K, Hotamisligil GS, Kurabayashi M
  • Journal Title: PLoS One Volume: 14;8 Issue: 11 Pages: e79386-e79386
  • DOI: 10.1371/journal.pone.0079386
  • Peer Reviewed
• [Journal Article] Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice (2013)
  • Author(s): Sunaga Hiroaki, Kurabayashi Masahiko
  • Journal Title: Nature Communications Volume: vol.4 Issue: 1 Pages: 2563-2563
  • DOI: 10.1038/ncomms3563
  • Peer Reviewed
• [Journal Article] Capillary endothelial fatty acid binding proteins 4 and 5 play a critical role in fatty acid uptake in heart and skeletal muscle (2013)
  • Author(s): Iso Tatsuya, Kurabayashi Masahiko
  • Journal Title: Arteriosclerosi Thrombosis and Vascular Biology Volume: vol.33 Issue: 11 Pages: 2549-2557
  • DOI: 10.1161/atvbaha.113.301588
  • Peer Reviewed
• [Journal Article] Palmitic Acid Induces Osteoblastic Differentiation in Vascular Smooth Muscle Cells through ACSL3 and NF-κB, Novel Targets of Eicosapentaenoic acid (2013)
  • Author(s): Kageyama A, Matsui H, 他7名
  • Journal Title: PLoS One Volume: 8(6) Issue: 6 Pages: e68197-e68197
  • DOI: 10.1371/journal.pone.0068197
  • Peer Reviewed
• [Journal Article] Attitudes toward interprofessional health care teams in undergraduate students and the alumni (2013)
  • Author(s): Makino T, Matsui H, 他14名
  • Journal Title: J Interprof Care Volume: 27(3) Issue: 3 Pages: 261-268
  • DOI: 10.3109/13561820.2012.751901
  • Peer Reviewed
• [Journal Article] Peroxisome Proliferator‐Activated Receptor‐γ in Capillary Endothelia Promotes Fatty Acid Uptake by Heart During Long‐Term Fasting (2013)
  • Author(s): Goto K, Iso T, Hanaoka H, Yamaguchi A, Suga T, Hattori A, Irie Y, Shinagawa Y, Matsui H, et al.
  • Journal Title: J Am Heart Assoc. Volume: 2(1) Issue: 1
  • DOI: 10.1161/jaha.112.004861
  • Peer Reviewed
• [Journal Article] Attitudes toward interprofessional health care teams in undergraduate students and the alumni (2013)
  • Author(s): Makino T, Shinozaki H, Hayashi K, Lee B, Matsui H, Kururi N, Kazama H, Ogawara H, Tozato F, Iwasaki K, Asakawa Y, Abe Y, Uchida Y, Kanaizumi S, Sakou K, Watanabe H
  • Journal Title: J Interprof Care. Volume: in press
  • Peer Reviewed
• [Journal Article] Pressure mediated hypertrophy and mechanical stretch up-regulate expression of the long form of leptin receptor (ob-Rb) in rat cardiac myocytes (2012)
  • Author(s): Matsui Hiroki, Kurabayashi Masahiko
  • Journal Title: BMC Cell Biology Volume: vol.13 Issue: 1 Pages: 37-37
  • DOI: 10.1186/1471-2121-13-37
  • Peer Reviewed
• [Journal Article] Attitudes of medical school deans towards interprofessional education in Western Pacific Region countries (2012)
  • Author(s): Lee B, Celletti F, Makino T, Matsui H, Watanabe H.
  • Journal Title: J Interprof Care. Volume: 26(6) Issue: 6 Pages: 479-83
  • DOI: 10.3109/13561820.2012.706336
  • Peer Reviewed
• [Journal Article] Stearoyl-CoA desaturase-1 (SCD1) augments saturated fatty acid-induced lipid accumulation and inhibits apoptosis in cardiac myocytes (2012)
  • Author(s): Matsui Hiroki, Kurabayashi Masahiko
  • Journal Title: PLoS One Volume: vol.7 Issue: 3 Pages: e33283-e33283
  • DOI: 10.1371/journal.pone.0033283
  • Peer Reviewed
• [Journal Article] Runx2/Smad3 Complex Negatively Regulates TGF-β-Induced Connective Tissue Growth Factor gene Expression in Vascular Smooth Muscle Cells (2012)
  • Author(s): Ohyama Yoshiaki, Kurabayashi Masahiko
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 19 Issue: 1 Pages: 23-35
  • DOI: 10.5551/jat.9753
  • NAID: 130004721900
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed
• [Journal Article] Notch induces myofibroblast differentiation of alveolar epithelial cells via transforming growth factor-{beta}-Smad3 pathway (2011)
  • Author(s): Aoyagi-Ikeda Kana, Kurabayashi Masahiko
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology Volume: vol45 Issue: 1 Pages: 136-144
  • DOI: 10.1165/rcmb.2010-0140oc
  • Peer Reviewed
• [Journal Article] Hypoxia-inducible factor-1αmediates TGF-β-induced PAI-1 production in alveolar macrophages in pulmonary fibrosis (2011)
  • Author(s): Ueno Manabu, Kurabayashi Masahiko
  • Journal Title: American Journal of Physiology-Lung Cellular and Molecular Physiology Volume: Vol.300 Issue: 5 Pages: L740-L752
  • DOI: 10.1152/ajplung.00146.2010
  • Peer Reviewed
• [Journal Article] Notch signaling pathway enhances bone morphogenetic protein 2 (BMP2) responsiveness of Msx2 gene to induce osteogenic differentiation and mineralization of vascular smooth muscle cells (2011)
  • Author(s): Shimizu Takehisa, Kurabayashi Masahiko
  • Journal Title: Journal of Biological Chemistry Volume: vol.286 Issue: 21 Pages: 19138-19148
  • DOI: 10.1074/jbc.m110.175786
  • Peer Reviewed
• [Presentation] Fatty acid binding protein 4 and 5 differentially regulate formation of abdominal aortic aneurysm induced by calcium chloride in mice (2014)
  • Author(s): 石井智晃、松井弘樹
  • Organizer: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-03-23
• [Presentation] Circulating FABP4 is released from adipocytes and capillary endothelial cells by sympathetic activation via beta3 receptor during acute cardiovascular event (2014)
  • Author(s): 河口智香、松井弘樹
  • Organizer: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-03-23
• [Presentation] Fatty Acid Binding Protein 4 is a direct target gene of Dll4-Notch1 pathway in Capillary Endothelial Cells in Heart (2014)
  • Author(s): 河口智香、松井弘樹
  • Organizer: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-03-23
• [Presentation] Effects of long chain fatty acid composition regulated by Elovl6 on the proliferation of vascular smooth muscle cells (2014)
  • Author(s): 安生早希、松井弘樹
  • Organizer: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-03-23
• [Presentation] 食事が血管依存性血管拡張反応(FMD)にもたらす影響について (2013)
  • Author(s): 松井弘樹
  • Organizer: 第20回日本未病システム学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-09
• [Presentation] 肺線維症における脂質代謝の変化と病態意義に関する検 (2013)
  • Author(s): 須永浩章、松井弘樹
  • Organizer: 第20回日本未病システム学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-09
• [Presentation] Fatty acid catalytic enzymes in vascular smooth muscle cells play a crucial role in the pathogenesis of atherosclerosis (2013)
  • Author(s): Matsui H
  • Organizer: European Society of Cardiology (ESC) Congress 2013
  • Place of Presentation: オランダ(アムステルダム)
  • Year and Date: 2013-09-02
• [Presentation] GPIHBP1, an endothelial binding site for lipoprotein lipase and chylomicrons, is induced by peroxisome proliferator-activated receptor gamma in cardiac fibroblasts (2013)
  • Author(s): 高橋宏明、松井弘樹
  • Organizer: 第77回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-16
• [Presentation] Differential expression of FABP4 and FABP5 isoforms in macrophages during the development of atherosclerosis (2013)
  • Author(s): 江ノ浦合位子、松井弘樹
  • Organizer: 第77回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-15
• [Presentation] Long-chain fatty acid elongase, Elovl6, is crucial for vascular smooth muscle cell proliferation underlying neointimal hyperplasia (2012)
  • Author(s): Sunaga H, Matsui H
  • Organizer: American Heart Association (AHA) Scientific Session 2012
  • Place of Presentation: アメリカ(ロサンゼルス)
  • Year and Date: 2012-11-05
• [Presentation] The role of Elovl6 in pulmonary fibrosis (2012)
  • Author(s): Sunaga H, Matsui H
  • Organizer: American Thoratic Society 2012 International Conference
  • Place of Presentation: アメリカ(サンフランシスコ)
  • Year and Date: 2012-11-05
• [Presentation] 肺の線維化におけるElovl6の病態意義 (2012)
  • Author(s): 須永浩章、松井弘樹
  • Organizer: 第52回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 2012-04-21
• [Presentation] Long-chain fatty acid elongase, Elovl6, is crucial for vascular smooth muscle cell proliferation underlying neointimal hyperplasia (2012)
  • Author(s): 須永浩章、松井弘樹
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2012-03-16
• [Presentation] Long-chain fatty acid elongase, Elovl6, is crucial for vascular smooth muscle cell proliferation underlying neointimal hyperplasia. (2012)
  • Author(s): 須永 浩章、松井 弘樹、他
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] 肺における脂質代謝の病態意義―遊離脂肪酸触媒酵素Elovl6と肺気腫との関連性について― (2011)
  • Author(s): 須永浩章、松井弘樹
  • Organizer: 第18回日本未病システム学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-11-19
• [Presentation] エイコサペンタエン酸は血管平滑筋細胞においてSmadシグナルを介してパルミチン酸による骨芽細胞分化を抑制する (2011)
  • Author(s): 影山藍子、松井弘樹
  • Organizer: 第59回日本心臓病学会総会・学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2011-09-24
• [Presentation] Eicosapentaenoic Acid Inhibits Palmitic Acid-Induced Osteogenic Differentiation by modulating Smad Signaling in Vascular Smooth Muscle Cells (2011)
  • Author(s): 影山藍子、松井弘樹
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2011-08-03
• [Presentation] Peroxisome Proliferator Activated Receptor-Alpha regulates Transendothelial Fatty Acid Transport in Capillary Endothelial Cells in Heart (2011)
  • Author(s): 入江康信、松井弘樹
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2011-08-03
• [Presentation] Elongation of long chain fatty acid member-6 protects from osteogenic differentiation and apoptosis in vascular smooth muscle cells (2011)
  • Author(s): 松井弘樹
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2011-08-03
• [Presentation] Eicosapentaenoic Acid Inhibits Palmitic Acid-Induced Osteogenic Differentiation by modulating Smad Signaling in Vascular Smooth Muscle Cells. (2011)
  • Author(s): 影山 藍子、松井 弘樹、他
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] Peroxisome Proliferator Activated Receptor-Alpha regulates Transendothelial Fatty Acid Transport in Capillary Endothelial Cells in Heart (2011)
  • Author(s): 入江 康徳、松井 弘樹、他
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] Elongation of long chain fatty acid member-6 protects from osteogenic differentiation and apoptosis in vascular smooth muscle cells (2011)
  • Author(s): 松井 弘樹、他
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] エイコサペンタエン酸は血管平滑筋細胞において Smadシグナルを介してパルミチン酸による骨芽細胞分化を抑制する (2011)
  • Author(s): 影山 藍子、松井 弘樹、他
  • Organizer: 第59回日本心臓病学会総会・学術集会
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Presentation] Fatty acid catalytic enzymes in vascular smooth muscle cells play a crucial role in the pathogenesis of atherosclerosis
  • Author(s): Hiroki Matsui, Tomoyuki Yokoyama, Hiroaki Sunaga, Saki Anjo, Tatsuya Iso, Masahiko Kurabayashi
  • Organizer: ESC Congress 2013
  • Place of Presentation: アムステルダム（オランダ）
• [Presentation] 肺線維症における脂質代謝の変化と病態意義に関する検討
  • Author(s): 須永 浩章, 松井 弘樹, 上野 学, 前野 敏孝, 磯 達也, 松坂 賢, 島野 仁, 横山 知行, 倉林 正彦
  • Organizer: 第20回日本未病システム学会学術総会
  • Place of Presentation: 学術総合センター(東京都)
• [Presentation] 食事が血管依存性血管拡張反応（FMD）にもたらす影響について
  • Author(s): 松井 弘樹, 石井 智晃, 河口 智香, 安生 早希, 須永 浩章, 横山 知行
  • Organizer: 第20回日本未病システム学会学術総会
  • Place of Presentation: 学術総合センター(東京都)
• [Presentation] Effects of long chain fatty acid composition regulated by Elovl6 on the proliferation of vascular smooth muscle cells.
  • Author(s): 安生 早希, 松井 弘樹, 須永 浩章, 磯 達也, 倉林 正彦, 横山 知行
  • Organizer: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京国際フォーラム（東京都）
• [Presentation] Fatty Acid Binding Protein 4 is a direct target gene of Dll4-Notch1 pathway in Capillary Endothelial Cells in Heart.
  • Author(s): 河口 智香, 磯 達也, 矢嶋 直人, 松井 弘樹, 横山 知行, 倉林 正彦
  • Organizer: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京国際フォーラム（東京都）
• [Presentation] Circulating FABP4 is released from adipocytes and capillary endothelial cells by sympathetic activation via beta3 receptor during acute cardiovascular event.
  • Author(s): 河口 智香, 磯 達也, 須永 浩章, Mas Rizky A.A Syamsunarno, 松井 弘樹, 大山 善昭, 横山 知行, 倉林 正彦
  • Organizer: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京国際フォーラム（東京都）
• [Presentation] Fatty acid binding protein 4 and 5 differentially regulate formation of abdominal aortic aneurysm induced by calcium chloride in mice.
  • Author(s): 石井 智晃, 磯 達也, Mas Rizky AA Syamsunarno, 須永 浩章, 松井 弘樹, 小板橋 紀通, 横山 知行, 倉林 正彦
  • Organizer: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京国際フォーラム（東京都）
• [Presentation] GPIHBP1, an endothelial binding site for lipoprotein lipase and chylomicrons, is induced by peroxisome proliferator-activated receptor-gamma in cardiac fibroblasts
  • Author(s): 高橋 宏明、磯 達也、松井 弘樹、横山 知行、倉林 正彦
  • Organizer: 第77回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] Differential expression of FABP4 and FABP5 isoforms in macrophages during the development of atherosclerosis.
  • Author(s): 江ノ浦 合位子、磯 達也、小倉 春海、松井 弘樹、横山 知行、倉林 正彦
  • Organizer: 第77回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] Long-chain fatty acid elongase, Elovl6, is crucial for vascular smooth muscle cell proliferation underlying neointimal hyperplasia.
  • Author(s): Hiroaki Sunaga, Hiroki Matsui, Saki Anjo, Tatsuya Iso, Masahiko Kurabayashi, Tomoyuki Yokoyama
  • Organizer: American Heart Association (AHA) Scientific Session 2012
  • Place of Presentation: ロサンゼルス（アメリカ合衆国）
• [Presentation] The role of Elovl6 in pulmonary fibrosis
  • Author(s): Hiroaki Sunaga, Hiroki Matsui, Manabu Ueno, Toshitaka Maeno, Takashi Matsuzaka, Hitoshi Shimano, Masahiko Kurabayashi, Tomoyuki Yokoyama
  • Organizer: American Thoratic Society 2012 International Conference
  • Place of Presentation: サンフランシスコ（アメリカ合衆国）
• [Presentation] 肺の線維化におけるElovl6の病態意義
  • Author(s): 須永 浩章, 松井 弘樹, 上野 学, 前野 敏孝, 竹村 仁男, 増渕 裕朗, 青木 史暁, 須賀 達夫, 松坂 賢, 島野 仁, 倉林 正彦, 横山 知行
  • Organizer: 第52回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Remarks] 群馬大学大学院保健学研究科 生体情報検査科学講座 横山研究室
  • URL: http://heart.health.gunma-u.ac.jp