Novel biomarker for atherosclerosis: clinical significance of isoprostanes analyzed by LC-MS/MS

• Project/Area Number: 17K09001
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Fukuoka University
• Principal Investigator: Segawa Namiko 福岡大学, 医学部, 准教授 (80352251)
• Co-Investigator(Kenkyū-buntansha): 安永 晋一郎 福岡大学, 医学部, 教授 (50336111) ; 朔 啓二郎 福岡大学, 医学部, 教授 (40183371) ; 三浦 伸一郎 福岡大学, 医学部, 教授 (20343709) ; ウォーターズ ブライアン 福岡大学, 医学部, 助教 (00609480) ; 今泉 聡 福岡大学, 医学部, 准教授 (60609478) ; 惠 淑萍 北海道大学, 保健科学研究院, 教授 (90337030)
• 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 動脈硬化 / リポ蛋白質 / 過酸化脂質 / 不飽和脂肪酸 / 酸化ストレス / 尿中イソプロスタン / LC-MS/MS / 多次元固相抽出 / イソプロスタン / プロスタグランジン / 固相抽出 / WHHLウサギ / アラキドン酸 / 糖尿病 / バイオマーカー / リポ蛋白 / プロテオーム / 質量分析 / 虚血性心疾患

Outline of Final Research Achievements

Oxidative stress is linked with many diseases including atherosclerosis and Alzheimer disease. Urine 8-isoprostaglandin F2α (8-iso-PGF2α) was established as a biomarker of oxidative stress. However, reactive oxygen species (ROS) affects the polyunsaturated fatty acid (PUFA) arachidonic acid to produces many isoforms of 8-iso-PGF2α, the biological significance of which is unclear. To explore the diagnosis marker of atherosclerosis, the relation between atherosclerosis and 8-iso-PGF2αisoforms was examined using multivariate data analysis methods including principal component analysis (PCA).

Academic Significance and Societal Importance of the Research Achievements

酸化ストレスは、動脈硬化、アルツハイマー型認知症などを含む多くの疾患と関連する。体内において不飽和脂肪酸が非酵素的に酸化され、産生された過酸化脂質産物のうち、尿中8-イソプロスタンが非侵襲的酸化ストレスのマーカーとして確立されている。しかし、尿中8-イソプロスタンの濃度が低いことが分析を困難にしている。多変量解析手法を用い、網羅的イソプロスタン解析をすることにより、より測定精度の高い疾患マーカーの確立につながることが期待される

Research Products

• [Journal Article] Associations of Perfluoroalkyl substances with blood lipids and Apolipoproteins in lipoprotein subspecies: the POUNDS-lost study (2020)
  • Author(s): Liu Gang、Zhang Bo、Hu Yang、Rood Jennifer、Liang Liming、Qi Lu、Bray George A.、DeJonge Lilian、Coull Brent、Grandjean Philippe、Furtado Jeremy D.、Sun Qi
  • Journal Title: Environmental Health Volume: 19 Issue: 1 Pages: 5-5
  • DOI: 10.1186/s12940-020-0561-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparison of Two Homogeneous LDL-Cholesterol Assays Using Fresh Hypertriglyceridemic Serum and Quantitative Ultracentrifugation Fractions (2019)
  • Author(s): Yano Megumi、Matsunaga Akira、Harada Sadako、Zhang Bo、Kawachi Emi、Tadera Mikiko、Saku Keijiro
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 26 Issue: 11 Pages: 979-988
  • DOI: 10.5551/jat.47191
  • NAID: 130007740419
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2019-11-01
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Replacing Dietary Monounsaturated Fat With Carbohydrate on HDL (High-Density Lipoprotein) Protein Metabolism and Proteome Composition in Humans (2019)
  • Author(s): Andraski Allison B.、Singh Sasha A.、Lee Lang Ho、Higashi Hideyuki、Smith Nathaniel、Zhang Bo、Aikawa Masanori、Sacks Frank M.
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: 39 Issue: 11 Pages: 2411-2430
  • DOI: 10.1161/atvbaha.119.312889
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of additional ablation of low‐voltage areas after Box isolation for persistent atrial fibrillation (2019)
  • Author(s): Kumagai Koichiro、Toyama Hideko、Zhang Bo
  • Journal Title: Journal of Arrhythmia Volume: 35 Issue: 2 Pages: 197-204
  • DOI: 10.1002/joa3.12169
  • Peer Reviewed / Open Access
• [Journal Article] Triglyceride deposit cardiomyovasculopathy: a rare cardiovascular disorder (2019)
  • Author(s): Li Ming、on behalf of the Japan TGCV study group、Hirano Ken-ichi、Ikeda Yoshihiko、Shimada Kazunori、et al.
  • Journal Title: Orphanet Journal of Rare Diseases Volume: 14 Issue: 1 Pages: 134-134
  • DOI: 10.1186/s13023-019-1087-4
  • Peer Reviewed / Open Access
• [Journal Article] Japanese Circulation Society with Resuscitation Science Study (JCS-ReSS) Group. Citizen bystander-patient relationship and 1-month outcomes after out-of-hospital cardiac arrest of cardiac origin from the All-Japan Utstein Registry: a prospective, nationwide, population-based, observational study. (2019)
  • Author(s): Suematsu Y, Zhang B, Kuwano T, Sako H, Ogawa M, Yonemoto N, Nonogi H, Kimura T, Nagao K, Yasunaga S, Saku K, Miura SI
  • Journal Title: BMJ Open Volume: 9 Issue: 7 Pages: e024715-e024715
  • DOI: 10.1136/bmjopen-2018-024715
  • Peer Reviewed / Open Access
• [Journal Article] Seminal plasma metabolome in relation to semen quality and urinary phthalate metabolites among Chinese adult men (2019)
  • Author(s): Wang Yi-Xin、Wu Yan、Chen Heng-Gui、Duan Peng、Wang Liang、Shen He-Qing、Lu Wen-Qing、Sun Bin、Wang Qi、Zhang Bo、Chavarro Jorge E.、Zhang Jie、Pan An
  • Journal Title: Environment International Volume: 129 Pages: 354-363
  • DOI: 10.1016/j.envint.2019.05.043
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of von Willebrand factor on coronary plaque burden in coronary artery disease patients treated with statins (2018)
  • Author(s): Kato Y, Iwata A, Futami M, Yamashita M, Imaizumi S, Kuwano T, Ike A, Sugihara M, Nishikawa H, Zhang B, Yasunaga S, Saku K, Miura SI
  • Journal Title: Medicine (Baltimore) Volume: 97 Issue: 17 Pages: e0589-e0589
  • DOI: 10.1097/md.0000000000010589
  • Peer Reviewed
• [Journal Article] Sex difference between target levels of cholesterol-related parameters and post-PCI long-term clinical outcomes: From the FU-Registry (2018)
  • Author(s): Matsuoka Yuta、Ike Amane、Ogawa Masahiro、Gondo Kouki、Shirai Kazuyuki、Sugihara Makoto、Nose Daisuke、Nishikawa Hiroaki、Iwata Atsushi、Kawamura Akira、Mori Ken、Zhang Bo、Yasunaga Shin’ichiro、Miura Shin-ichiro、Saku Keijiro
  • Journal Title: Journal of Cardiology Volume: 71 Issue: 3 Pages: 259-267
  • DOI: 10.1016/j.jjcc.2017.09.011
  • Peer Reviewed / Open Access
• [Journal Article] Impact of the triglyceride level on coronary plaque components in female patients with coronary artery disease treated with statins (2018)
  • Author(s): Yamashita M, Iwata A, Kato Y, Futami M, Imaizumi S, Kuwano T, Ike A, Sugihara M, Nishikawa H, Zhang B, Yasunaga S, Saku K, Miura SI
  • Journal Title: Heart and Vessels Volume: 33 Issue: 10 Pages: 1175-1184
  • DOI: 10.1007/s00380-018-1173-x
  • Peer Reviewed
• [Journal Article] Tricaprin Rescues Myocardial Abnormality in a Mouse Model of Triglyceride Deposit Cardiomyovasculopathy (2018)
  • Author(s): Suzuki A, Yamaguchi S, Li M, Hara Y, Miyauchi H, Ikeda Y, Zhang B, Higashi M, Ikeda Y, Takagi A, Nagasaka H, Kobayashi K, Magata Y, Aoyama T, Hirano KI
  • Journal Title: Journal of Oleo Science Volume: 67 Issue: 8 Pages: 983-989
  • DOI: 10.5650/jos.ess18037
  • NAID: 130007429329
  • ISSN: 1345-8957, 1347-3352
  • Peer Reviewed
• [Journal Article] Association between discordance of LDL-C and non-HDL-C and clinical outcomes in patients with stent implantation: from the FU-Registry (2017)
  • Author(s): Shiiba Michiyo、Zhang Bo、Miura Shin-ichiro、Ike Amane、Nose Daisuke、Kuwano Takashi、Imaizumi Satoshi、Sugihara Makoto、Iwata Atushi、Nishikawa Hiroaki、Kawamura Akira、Shirai Kazuyuki、Yasunaga Shin’ichiro、Saku Keijiro
  • Journal Title: Heart and Vessels Volume: 33 Issue: 2 Pages: 102-112
  • DOI: 10.1007/s00380-017-1036-x
  • Peer Reviewed / Open Access
• [Journal Article] Effects of dipeptidyl peptidase-4 inhibitor sitagliptin on coronary atherosclerosis as assessed by intravascular ultrasound in type 2 diabetes mellitus with coronary artery disease (2017)
  • Author(s): Yuta Kato,Atsushi Iwata, Bo Zhang, Shin-ichiro Miura, Satoshi Imaizumi, Takashi Kuwano, Amane Ike, Makoto Sugihara, Hiroaki Nishikawa, Shin'ichiro Yasunaga, Keijiro Sakua
  • Journal Title: IJC Metabolic & Endocrine Volume: 16 Pages: 1-9
  • DOI: 10.1016/j.ijcme.2017.06.005
  • Peer Reviewed / Open Access
• [Journal Article] Is a bare-metal stent still useful for improving the outcome of percutaneous coronary intervention? From the FU-Registry (2017)
  • Author(s): GONDO, K., IKE, A., OGAWA, M., SHIRAI, K., SUGIHARA, M., NISHIKAWA, H., IWATA, A., KAWAMURA, A., MORI, K., ZHANG, B., MIURA, S., YASUNAGA, S. & SAKU, K.
  • Journal Title: J Cardiol Volume: 69 Issue: 4 Pages: 652-659
  • DOI: 10.1016/j.jjcc.2016.06.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of the antithrombotic abilities of non-vitamin K antagonist oral anticoagulants using the Total Thrombus-formation Analysis System(R) (2017)
  • Author(s): IDEMOTO, Y., MIURA, S. I., NORIMATSU, K., SUEMATSU, Y., HITAKA, Y., SHIGA, Y., MORII, J., IMAIZUMI, S., KUWANO, T., IWATA, A., ZHANG, B., OGAWA, M. & SAKU, K.
  • Journal Title: Heart Vessels Volume: 32 Issue: 3 Pages: 309-316
  • DOI: 10.1007/s00380-016-0864-4
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Pitfalls of diagnosing urinary tract infection in infants and young children (2017)
  • Author(s): Yamasaki Y, Uemura O, Nagai T, Yamakawa S, Hibi Y, Yamamoto M, Nakano M, Kasahara K, Bo Zhang.
  • Journal Title: Pediatr Int Volume: 59 Issue: 7 Pages: 786-792
  • DOI: 10.1111/ped.13292
  • Peer Reviewed
• [Presentation] Unsaturated Fat Replacing Carbohydrate or Protein Affects Protein-based HDL Subspecies of Different Functionality (2019)
  • Author(s): Zhang B
  • Organizer: American Heart Association Scientific Session, EPI/Lifestyle 2019
  • Int'l Joint Research
• [Presentation] Unsaturated Fat Replacing Carbohydrate or Protein Affects Protein-based HDL Subspecies of Different Functionality (2019)
  • Author(s): Bo Zhang, Barry Guglielmo, Jeremy D Furtado, Frank M Sacks
  • Organizer: American Heart Association, EPI/Lifestyle 2019 Scientific Sessions
  • Int'l Joint Research
• [Presentation] Effects of CNT-01 on the Composition of Lipids in Lipoproteins Produced from the Small Intestine in Mice (2019)
  • Author(s): Bo Zhang , Satoshi Yamaguchi , Ken-ichi Hirano
  • Organizer: 中性脂肪学会第１回学術集会