Development of pioneering therapy for early atherosclerosis using novel S1P donor

• Project/Area Number: 22590139
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Nagoya City University
• Principal Investigator: FUJII Satoshi 名古屋市立大学, 大学院・薬学研究科, 教授 (90291228)
• Co-Investigator(Kenkyū-buntansha): OZEKI Tetsuya 名古屋市立大学, 大学院・薬学研究科, 教授 (60277259) ; DOHI Yasuaki 名古屋市立大学, 大学院・薬学研究科, 准教授 (40305529)
• Co-Investigator(Renkei-kenkyūsha): IWAKI Soichiro 名古屋市立大学, 大学院・薬学研究科, 講師 (60399962) ; SUGIURA Tomonori 名古屋市立大学, 大学院・薬学研究科, 助教 (60535235)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 生理活性 / 脂質 / 薬学 / 臨床 / 内皮前駆細胞 / 動脈硬化症 / ナノ粒子 / HDL

Research Abstract

A novel strategy for conquering atherosclerosis is desirable. Athero-protective HDL is rich in bioactive lipid, sphingosine-1-phosphate (S1P). The effect of S1P on vascular endothelial cells was clarified. The relationship between plasma S1P and vascular endothelial function was evaluated. A newly synthesized biomimetic HDL nanoparticle rich in both S1P and apoA1 exhibited promising anti-inflammatory effects on endothelial cells in culture and on mice challenged with LPS.

Research Products

• [Journal Article] Natural killer T cells are required for lipopolysaccharide-mediated enhancement of atherosclerosis in apolipoprotein E-deficient mice (2013)
  • Author(s): Andoh Y, Ogura H, Satoh M, Shimano K, Okuno H, Fujii S, Ishimori N, Eshima K, Tamauchi H, Otani T, Nakai Y, Van Kaer L, Tsutsui H, Onoe K, Iwabuchi K
  • Journal Title: Immunobiology Volume: 218 Issue: 4 Pages: 561-569
  • DOI: 10.1016/j.imbio.2012.07.022
  • Peer Reviewed
• [Journal Article] The Relation between habitual sleep duration and blood pressure values in Japanese male subjects. (2013)
  • Author(s): Satoh H, Fujii S, Tsutsui H.
  • Journal Title: Environment Health and Preventive Medicine Volume: 18 Issue: 3 Pages: 215-20
  • DOI: 10.1007/s12199-012-0309-3
  • NAID: 10031175982
  • Peer Reviewed
• [Journal Article] Cigarette Smoking Induces Vascular Damage and Persistent Elevation of Plasma Serotonin Unresponsive to 8 Weeks of Smoking Cessation. (2013)
  • Author(s): Sugiura T, Dohi Y, Hirowatari Y, Yamashita S, Ohte N, Kimura G, Fujii S.
  • Journal Title: Int J Cardiol Volume: 166 Pages: 748-749
  • Peer Reviewed
• [Journal Article] Sphingosine kinase 1 expression is downregulated during differentiation of Friend cells due to decreased c-MYB. (2013)
  • Author(s): Mizutani N, Kobayashi M, Sobue S, Ichihara M, Ito H, Tanaka K, Iwaki S,Fujii S,Ito Y, Tamiya-Koizumi K, Takagi A, Kojima T, Naoe T, Suzuki M, Nakamura M, Banno Y, Nozawa Y, Murate T.
  • Journal Title: Biochimica et Biophysica Acta -Molecular Cell Research Volume: 1833 Issue: 5 Pages: 1006-16
  • DOI: 10.1016/j.bbamcr.2013.01.001
  • Peer Reviewed
• [Journal Article] Cigarette Smoking Induces Vascular Damage and Persistent Elevation of Plasma Serotonin Unresponsive to 8 Weeks of Smoking Cessation (2013)
  • Author(s): Sugiura T
  • Journal Title: International Journal of Cardiology Volume: in press
  • Peer Reviewed
• [Journal Article] Sphingosine kinase 1 expression is downregulated during differentiation of Friend cells due to decreased c-MYB. (2013)
  • Author(s): Mizutani N
  • Journal Title: Biochimica et Biophysica Acta - Molecular Cell Research Volume: 1833 Pages: 1006-1016
  • Peer Reviewed
• [Journal Article] Decreased glomerular filtration rate is a significant and independent risk for in-hospital mortality in Japanese patients with acute myocardial infarction. (2012)
  • Author(s): Satoh H, Kawashima N, Ishimori N, Urasawa K, Fujii S, Tsutsui H.
  • Journal Title: Hypertens Res Volume: 35 Issue: 4 Pages: 463-469
  • DOI: 10.1038/hr.2011.224
  • Peer Reviewed
• [Journal Article] Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue inflammation, steatohepatitis and insulin resistance (2012)
  • Author(s): Satoh, M., Andoh, Y., Clingan, S. C., Ogura, H., Fujii, S., Nakayama, T., Taniguchi, M., Hirata, N., Ishimori, N., Tsutsui, H., Onoe, K. Iwabuchi, K
  • Journal Title: PLoS ONE Volume: 7(2) Issue: 2 Pages: 1-12
  • DOI: 10.1371/journal.pone.0030568
  • NAID: 120004043739
  • Peer Reviewed
• [Journal Article] Analytical evaluation of plasma serotonin and sphingosine 1-phosphate and their clinical assessment in early atherosclerosis (2012)
  • Author(s): Tomonori Sugiura
  • Journal Title: Coron.Artery Dis. Volume: (印刷中) Issue: 4 Pages: 234-238
  • DOI: 10.1097/mca.0b013e328351ab0a
  • Peer Reviewed
• [Journal Article] Role of down-regulated neutral ceramidase during all-trans retinoic acid induced neuronal differentiation in SH-SY5Y neuroblastoma cells (2012)
  • Author(s): Kouji Tanaka
  • Journal Title: J.Biochem. Volume: (印刷中) Issue: 6 Pages: 611-620
  • DOI: 10.1093/jb/mvs033
  • Peer Reviewed
• [Journal Article] Staphylococcal superantigen-like protein 3 binds to the Toll-like receptor 2 extracellular domain and inhibits cytokine production induced by Staphylococcus aureus, cell wall component, or lipopeptides in murine macrophages. (2012)
  • Author(s): Yokoyama R, Itoh S, Kamoshida G, Takii T, Fujii S, Tsuji T, Onozaki K.
  • Journal Title: Infect Immun. Volume: 80(8) Issue: 8 Pages: 2816-25
  • DOI: 10.1128/iai.00399-12
  • Peer Reviewed
• [Journal Article] Posttranscriptional regulation of expression of plasminogen activator inhibitor type-1 by sphingosine 1-phosphate in HepG2 liver cells. (2012)
  • Author(s): Iwaki S, Yamamura S, Asai M, Sobel BE, Fujii S.
  • Journal Title: Biochimica et Biophysica Acta Volume: 1819 Pages: 1132-1141
  • Peer Reviewed
• [Journal Article] Expression of circulating microRNA-126 in patients with coronary artery disease: correlation with LDL cholesterol. (2012)
  • Author(s): Sun X, Zhang M, Sanagawa A, Mori C, Ito S, Iwaki S, Satoh H, Fujii S.
  • Journal Title: Thromb J Volume: 10(1) Issue: 1 Pages: 16-16
  • DOI: 10.1186/1477-9560-10-16
  • Peer Reviewed
• [Journal Article] Analytical evaluation of plasma serotonin and sphingosine 1-phosphate and their clinical assessment in early atherosclerosis (2012)
  • Author(s): Sugiura T
  • Journal Title: Coronary Artery Disease Volume: 23 Pages: 234-238
  • Peer Reviewed
• [Journal Article] Role of down-regulated neutral ceramidase during all-trans retinoic acid induced neuronal differentiation in SH-SY5Y neuroblastoma cells (2012)
  • Author(s): Tanaka K
  • Journal Title: Journal of Biochemistry Volume: 151 Pages: 611-620
  • Peer Reviewed
• [Journal Article] Posttranscriptional regulation of expression of plasminogen activator inhibitor type-1 by sphingosine 1-phosphate in HepG2 liver cells. Biochimica et Biophysica Acta (2012)
  • Author(s): Iwaki S
  • Journal Title: Biochimica et Biophysica Acta Volume: 1819 Pages: 1132-1141
  • Peer Reviewed
• [Journal Article] Modulators of induction of plasminogen activator inhibitor type-1 in HepG2 cells by transforming growth factor-β (2011)
  • Author(s): Naomi Nakayama
  • Journal Title: Coron.Artery Dis. Volume: 22 Issue: 7 Pages: 468-478
  • DOI: 10.1097/mca.0b013e32834a3817
  • Peer Reviewed
• [Journal Article] Physicochemical properties of macrogol ointment and emulsion ointment blend developed for regulation of water absorption (2011)
  • Author(s): Noda Y, Watanabe K, Sanagawa A, Sobajima Y, Fujii S.
  • Journal Title: Int J Pharmaceut Volume: 419 Issue: 1-2 Pages: 131-136
  • DOI: 10.1016/j.ijpharm.2011.07.034
  • Peer Reviewed
• [Journal Article] Posttranscriptional regulation of expression of plasminogen activator inhibitor type-1 by cAMP in HepG2 liver cells (2011)
  • Author(s): Takefumi Asakura
  • Journal Title: J.Biochem. Volume: 150 Issue: 6 Pages: 687-694
  • DOI: 10.1093/jb/mvr110
  • Peer Reviewed
• [Journal Article] an anion exchange resin agent, can rapidly decrease the number of LDL particles without affecting their sizes in patients with hyperlipidemia. (2010)
  • Author(s): Kishimoto N, Fujii S, Chiba H, Sakuma I, Tsutsui H. Cholestimide
  • Journal Title: J Cardiology Volume: 55 Issue: 1 Pages: 65-68
  • DOI: 10.1016/j.jjcc.2009.08.006
  • Peer Reviewed
• [Journal Article] Natural Killer T cells are involved in adipose tissues inflammation and glucose intolerance in diet-induced obese mice. (2010)
  • Author(s): Ohmura K, Ishimori N, Ohmura Y, Tokuhara S, Nozawa A, Horii S, Andoh Y, Fujii S, Iwabuchi K, Onoe K, Tsutsui H.
  • Journal Title: Arterioscl Thromb Vasc Biol Volume: 30 Issue: 2 Pages: 193-199
  • DOI: 10.1161/atvbaha.109.198614
  • NAID: 120002261714
  • Peer Reviewed
• [Journal Article] Increased expression of plasminogen activator inhibitor type-1 (PAI-1) in HEPG2 cells induced by insulin mediated by the 3'-untranslated region of the PAI-1 gene and its pharmacologic implications. (2010)
  • Author(s): Miyagawa R, Asakura T, Nakamura T, Okada H, Iwaki S, Sobel, B, Fujii S.
  • Journal Title: Cor Art Dis Volume: 21 Issue: 3 Pages: 144-50
  • DOI: 10.1097/mca.0b013e328335790e
  • Peer Reviewed
• [Journal Article] Waist circumference can predict the occurrence of multiple metabolic risk factors in middle-aged Japanese subjects. (2010)
  • Author(s): Satoh H, Fujii S, Furumoto T, Kishi R, Tsutsui H.
  • Journal Title: Industrial Health Volume: 48 Pages: 447-451
  • NAID: 40017252246
  • URL: https://www.jstage.jst.go.jp/article/indhealth/48/4/48_MS1121/_article
  • Peer Reviewed
• [Journal Article] Critical role of water diffusion into matrix in external use iodine preparations. (2010)
  • Author(s): Noda Y, Fujii S.
  • Journal Title: International Journal of Pharmaceutics Volume: 394 Issue: 1-2 Pages: 85-91
  • DOI: 10.1016/j.ijpharm.2010.05.009
  • Peer Reviewed
• [Journal Article] Increased expression of PAI-1 in HepG2 cells induced by insulin mediated by the 3'-untranslated region of the PAI-1 gene and its pharmacologic implications. (2010)
  • Author(s): Miyagawa R, Asakura T, Nakamura T, Okada H, Iwaki S, Sobel B, Fujii S.2010
  • Journal Title: Coronary Artery Disease Volume: 21 Pages: 144-150
  • Peer Reviewed
• [Journal Article] Physicochemical characterization of tretinoin tocoferil emulsion and povidone-iodine sugar ointment blend developed for improved regulation of wound moisture.
  • Author(s): Noda Y, Saito M, Watanabe K, Sanagawa A, Sobajima Y, Fujii S.
  • Journal Title: Chem Pharm Bull Volume: (in press)
  • NAID: 130003360805
  • URL: https://www.jstage.jst.go.jp/article/cpb/advpub/0/advpub_c13-00186/_article
  • Peer Reviewed
• [Presentation] 炎症誘導モデルマウスに対する人工HDL金ナノ粒子製剤の抗炎症効果 (2013)
  • Author(s): 高橋 朋弘、田上 辰秋、 岩城 壮一郎、藤井 聡、 尾関 哲也
  • Organizer: 第29回日本DDS学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2013-07-04
• [Presentation] 低酸素環境においてスフィンゴ脂質が線溶系に与える分子機構の解析 (2013)
  • Author(s): 藤井 聡、真川 明将、岩城 壮一郎、浅井 萌子、榊原 大輔、山村 周平
  • Organizer: 第35回日本血栓止血学会学術集会
  • Place of Presentation: 山形
  • Year and Date: 2013-06-01
• [Presentation] S1Pが血液線溶系に与える影響の解明 (2013)
  • Author(s): 真川明将, 岩城壮一郎, 浅井萌子, 榊原大輔, 山村周平, 藤井聡
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-28
• [Presentation] Circulating MicroRNA-126 as a Potential Biomarker for Recovery from Smoking-Related Endothelial Damage. (2012)
  • Author(s): Sugiura T, Dohi Y, Yamashita S, Ohte N, Sanagawa A, Ito S, Iwaki S, Fujii S, Ohkawa R, Yatomi Y, Kimura G.
  • Organizer: Scientific Session of the American Heart Association.
  • Place of Presentation: Los Angeles, USA
  • Year and Date: 2012-11-07
• [Presentation] Increased plasma sphyingosine-1-phosphate (S1P) and its capacity to increase expression of PAI-1 in adipocytes and obese subjects. (2012)
  • Author(s): Fujii S, Nagasaki A, Ito S, Iwaki S, Sobel B, Ohkawa R, Mishima Y, Yatomi Y, Furumoto T.
  • Organizer: Scientific Session of the American Heart Association.
  • Place of Presentation: Los Angeles, USA
  • Year and Date: 2012-11-06
• [Presentation] ABC transporters can mediate extracellular release of S1P in adipocytes under hypoxia: implications for atherothrombosis in obesity. (2012)
  • Author(s): Ayako Nagasaki, Yuichiro Yuda, Keiko Koike, Soichiro Iwaki, Satoshi Fujii
  • Organizer: 7th Congres of the Asian-Pacific Society on Thrombosis and Hemostasis.
  • Place of Presentation: Melbourne, Australia.
  • Year and Date: 2012-10-29
• [Presentation] Functional Engineered Nano-sized Particles and Their Pharmaceutical Applications (2012)
  • Author(s): Tomohiro Takahashi, Tatsuaki Tagami, Satoshi Fujii, Soichiro Iwaki, Ryohei Ito, Hiroshi Yanai, Tetsuya Ozeki
  • Organizer: 10th France - Japan DDS Symposium
  • Place of Presentation: Bordeaux, France
  • Year and Date: 2012-10-11
• [Presentation] S1P/ApoA1 搭載金ナノ粒子による血管内皮細胞に対する抗炎症効果の検討 (2012)
  • Author(s): 高橋 朋弘、田上 辰秋、 岩城 壮一郎、藤井 聡、尾関 哲也
  • Organizer: 第28回日本 DDS学会年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-07-04
• [Presentation] 金ナノ粒子を核とした人工 HDL ナノ粒子の調製と物性評価 (2012)
  • Author(s): 高橋 朋弘、 田上 辰秋、 岩城 壮一郎、 藤井 聡、 尾関 哲也
  • Organizer: 日本薬剤学会 第27回年会
  • Place of Presentation: 神戸
  • Year and Date: 2012-05-24
• [Presentation] A novel HDL-like gold nanoparticles formulation with anti-inflammatory effect on vascular endothelial cells. (2012)
  • Author(s): Tomohiro Takahashi, Tatsuaki Tagami, Soichiro Iwaki, Satoshi Fujii, Tetsuya Ozeki.
  • Organizer: AAPS Annual Meeting and Exposition
  • Place of Presentation: Chicago, USA
• [Presentation] Increased plasma sphyingosine-1-phosphate(S1P) and its capacity to increase expression of PAI-1 in adipocytes and obese subjects. (2012)
  • Author(s): Satoshi Fujii
  • Organizer: 米国心臓協会学術集会
  • Place of Presentation: Los Angeles, USA
• [Presentation] 血清除去刺激におけるSphingosine kinaseの発現調節機序 (2012)
  • Author(s): 水谷 直貴
  • Organizer: 第85回 日本生化学大会
  • Place of Presentation: 福岡
• [Presentation] Statin-Induced Improvement of Human Endothelial Function is Mediated by Sphingosine 1-Phosphate. (2011)
  • Author(s): Tomonori Sugiura, Yasuaki Dohi, Sumiyo Yamashita, Nobuyuki Ohte, Shiori Ito, Chieko Mori, Soichiro Iwaki, Yuji Hirowatari, Ryunosuke Ohkawa, Yuko Mishima, Yutaka Yatomi, Genjiro Kimura, Satoshi Fujii.
  • Organizer: Scientific Session of the American Heart Association.
  • Place of Presentation: Orlando, USA
  • Year and Date: 2011-11-15
• [Presentation] Statin-induced improvement of human endothelial function is mediated by sphingosine 1-phosphate (2011)
  • Author(s): Sugiura T, Dohi Y, Fujii S, et al
  • Organizer: American Heart Association Annual Scientific Session
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 2011-11-15
• [Presentation] Imbalance Between Plasma Serotonin and Sphingosine 1-Phosphate Is a Novel Therapeutic Target of Statins in Patients with Early Atherosclerosis. (2010)
  • Author(s): Sugiura T, Dohi Y, Yamashita S, Ohte N, Mori C, Hirowatari Y, Ohkawa R, Mishima Y, Yatomi Y, Kimura G, Fujii S.
  • Organizer: Scientific Session of the American Heart Association.
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-15
• [Presentation] Imbalance Between Plasma Serotonin and Sphingosine 1-Phosphate Is a Novel Therapeutic Target of Statins in Patients with Early Atherosclerosis. (2010)
  • Author(s): Sugiura T, Dohi Y, Yatomi Y, Kimura G, Fujii S, et al.
  • Organizer: 2010 Scientific Session of the American Heart Association.
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-15
• [Presentation] Hypoxia Enhances S1P Release From Adipocytes and Provokes S1P-mediated Insulin Resistance by Inducing TNF-α Expression in Adipose NKT Cells. (2010)
  • Author(s): Fujii S, Ito S, Koike K, Iwaki S, Iwabuchi K, Ohkawa R, Mishima Y, Yatomi Y, Furumoto T.
  • Organizer: Scientific Session of the American Heart Association.
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-14
• [Presentation] Sphingosine 1-phosphate is a bioactive lipid that confers high-density lipoprotein with vascular protection mediated by endothelium-dependent vasodilation (2010)
  • Author(s): Sugiura T, Dohi Y, Yamashita S, Ohkawa R, Yatomi Y, Kimura G, Fujii S.
  • Organizer: European Society of Cardiology Congress 2010
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2010-08-29
• [Presentation] Sphingosine 1-phosphate is a bioactive lipid that confers high-density lipoprotein with vascular protection mediated byendothelium-dependent vasodilation (2010)
  • Author(s): Sugiura T, Dohi Y, Yamashita S, Kimura G, Mishima Y, Ohkawa R, Yatomi Y, Fujii S.
  • Organizer: 第42回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 岐阜
  • Year and Date: 2010-07-15
• [Remarks]
  • URL: http://www.phar.nagoya-cu.ac.jp/hp/szg/index.html
• [Remarks] 名古屋市立大学大学院薬学研究科医療薬学講座病態解析分野
  • URL: http://www.phar.nagoya-cu.ac.jp/hp/szg/publication.html
• [Remarks] 名古屋市立大学大学院薬学研究科
  • URL: http://www.nagoya-cu.ac.jp/phar/1.htm
• [Remarks]
  • URL: http://www.phar.nagoya-cu.ac.jp/research_course/res_course16.html
• [Remarks]
  • URL: http://www.phar.nagoya-cu.ac.jp/hp/szg/index.html