Exploring the pathophysiology of dyslipidemia using cITP lipoprotein analysis

• Project/Area Number: 23590699
• 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): SAKU Keijiro 福岡大学, 医学部, 教授 (40183371) ; MATSUNAGA Akira 福岡大学, 医学部, 教授 (60221587) ; MIURA Shin-ichiro 福岡大学, 医学部, 准教授 (20343709)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: リポ蛋白質分析 / 脂質異常症 / キャピラリー等速電気泳動法 / 低HDL-C血症 / HDL治療 / 合成HDL / LDL亜分画 / HDL亜分画 / 心不全 / リポ蛋白質 / キャピラリー等速電気泳動 / スタチン / リポ蛋白亜分画 / 慢性心不全 / 腹部脂肪組織 / 動物実験

Outline of Final Research Achievements

High-density lipoprotein (HDL) has anti-atherogenic properties. Capillary isotachophoresis (cITP) separates plasma lipoproteins into 3 HDL subfractions and 3 LDL subfractions. In the present study, first, we show that that cITP lipoprotein analysis is useful in the differential diagnosis of hypoalphalipoproteinemia (HA). Next, we show that recombinant HDL (a complex of apolipoprotein AI mimetic peptide and phospholipids) had a significant effect on the remodeling of LDL subfractions in WHHL rabbits, an animal model of human familial hypercholesterolemia, indicating that remodeling effects on LDL subfractions is one of the mechanisms of the anti-atherogenic effects of recombinant HDL. Finally, we found that in female subjects with increased visceral fat, the subcutaneous fat area is associated with cITP sHDL, indicating that subcutaneous fat may have an effect on HDL metabolism.

Research Products

• [Journal Article] Associations between different types of hypoglycemic agents and the clinical outcome of percutaneous coronary intervention in diabetic patients-From the FU-Registry (2015)
  • Author(s): Ike A, Shirai K, Nishikawa H, Iwata A, Yahiro E, Sugihara M, Kawamura A, Uehara Y, Zhang B, Ogawa M, Mori K, Miura SI, Saku K
  • Journal Title: J Cardiol Volume: 65 Issue: 5 Pages: 390-396
  • DOI: 10.1016/j.jjcc.2014.06.012
  • Peer Reviewed
• [Journal Article] Associations between lipid profiles and MACE in hemodialysis patients with percutaneous coronary intervention: from the FU-Registry (2015)
  • Author(s): Nagata I, Ike A, Nishikawa H, Zhang B, Sugihara M, Mori K, Iwata A, Kawamura A, Shirai K, Uehara Y, Ogawa M, Miura S, Saku K
  • Journal Title: J Cardiol Volume: 65 Issue: 2 Pages: 05-111
  • DOI: 10.1016/j.jjcc.2014.03.016
  • Peer Reviewed
• [Journal Article] Associations between the consumption of different kinds of seafood and out-of-hospital cardiac arrests of cardiac origin in Japan (2014)
  • Author(s): Suematsu Y, Miura S, Zhang B, Uehara Y, Tokunaga M, Yonemoto N, Nonogi H, Nagao K, Kimura M, Saku K
  • Journal Title: IJC Heart & Vessels Volume: 2 Pages: 8-14
  • DOI: 10.1016/j.ijchv.2013.11.002
  • Peer Reviewed / Open Access
• [Journal Article] Rosuvastatin activates ATP-binding cassette transporter A1-dependent efflux ex vivo and promotes reverse cholesterol transport in macrophage cells in mice fed a high-fat diet (2014)
  • Author(s): Shimizu T, Miura S, Tanigawa H, Kuwano T, Zhang B, Uehara Y, Saku K
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 34 Issue: 10 Pages: 2246-2253
  • DOI: 10.1161/atvbaha.114.303715
  • Peer Reviewed / Open Access
• [Journal Article] Impact of cigarette smoking cessation on high-density lipoprotein functionality (2014)
  • Author(s): Takata K, Imaizumi S, Kawachi E, Suematsu Y, Shimizu T, Abe S, Matsuo Y, Tsukahara H, Noda K, Yahiro E, Zhang B, Uehara Y, Miura S, Saku K
  • Journal Title: Circ J Volume: 78 Pages: 2955-2962
  • Peer Reviewed
• [Journal Article] Early onset and focal spike discharges as indicators of poor prognosis for myoclonic-astatic epilepsy (2014)
  • Author(s): Inoue T, Ihara Y, Tomonoh Y, Nakamura N, Ninomiya S, Fujita T, Ideguchi H, Yasumoto S, Zhang B, Hirose S
  • Journal Title: Brain Dev Volume: 36 Issue: 7 Pages: 613-619
  • DOI: 10.1016/j.braindev.2013.08.009
  • Peer Reviewed
• [Journal Article] Selective evaluation of high density lipoprotein from mouse small intestines by an in situ perfusion technique (2014)
  • Author(s): Yamaguchi S, Zhang B, Tomonaga T, Seino U, Kanagawa A, Nagasaka H, Suzuki A, Miida T, Yamada S, Sasaguri Y, Doi T, Saku K, Okazaki M, Tochino Y, Hirano K
  • Journal Title: J Lipid Res Volume: 55 (5) Issue: 5 Pages: 905-18
  • DOI: 10.1194/jlr.m047761
  • Peer Reviewed
• [Journal Article] Association of nonsense mutation in GABRG2 with abnormal trafficking of GABA receptors in severe epilepsy (2014)
  • Author(s): Ishii, A., Kanaumi, T., Sohda, M., Misumi, Y., Zhang, B., Kakinuma, N., Haga, Y., Watanabe, K., Takeda, S., Okada, M., Ueno, S., Kaneko, S., Takashima, S., Hirose, S.
  • Journal Title: Epilepsy Res Volume: 108 Issue: 3 Pages: 420-432
  • DOI: 10.1016/j.eplepsyres.2013.12.005
  • Peer Reviewed
• [Journal Article] Therapeutic approaches to the regulation of metabolism of high-density lipoprotein. Novel HDL-directed pharmacological intervention and exercise. (2013)
  • Author(s): Zhang, B., E. Kawachi, S. Miura, Y. Uehara, A. Matsunaga, M. Kuroki, and K. Saku.
  • Journal Title: Circ J Volume: 77 Pages: 2651-2663
  • NAID: 10031196810
  • Peer Reviewed
• [Journal Article] FAMP, a novel apoA-I mimetic peptide, suppresses aortic plaque formation through promotion of biological HDL function in ApoE-deficient mice. (2013)
  • Author(s): Uehara, Y., S. Ando, E. Yahiro, K. Oniki, M. Ayaori, S. Abe, E. Kawachi, B. Zhang, S. Shioi, H. Tanigawa, S. Imaizumi, S. Miura, and K. Saku.
  • Journal Title: J Am Heart Assoc Volume: 2 Issue: 3
  • DOI: 10.1161/jaha.113.000048
  • Peer Reviewed
• [Journal Article] A human Dravet syndrome model from patient induced pluripotent stem cells. (2013)
  • Author(s): Higurashi N, Uchida T, Lossin C, Misumi Y, Okada Y, Akamatsu W, Imaizumi Y, Zhang B, Nabeshima K, Mori MX, Katsurabayashi S, Shirasaka Y, Okano H, Hirose S.
  • Journal Title: Mol Brain Volume: 6 Issue: 1 Pages: 19-19
  • DOI: 10.1186/1756-6606-6-19
  • Peer Reviewed
• [Journal Article] Reactivity of direct assays for low-density lipoprotein (LDL) cholesterol toward charge-modified LDL in hypercholesterolemia (2012)
  • Author(s): Zhang, B., Kawachi, E., Matsunaga, A., Imaizumi, S., Noda, K., Uehara, Y., Miura, S., Yoshinaga, K., Kuroki, M., Saku, K.
  • Journal Title: Circ J Volume: 76 Pages: 2241-8
  • NAID: 10030697012
  • Peer Reviewed
• [Journal Article] Lifestyle changes through the use of delivered meals and dietary counseling in a single-blind study. The STYLIST study (2012)
  • Author(s): Noda, K., Zhang, B., Iwata, A., Nishikawa, H., Ogawa, M., Nomiyama, T., Miura, S., Sako, H., Matsuo, K., Yahiro, E., Yanase, T., Saku, K.
  • Journal Title: Circ J Volume: 76 Pages: 1335-44
  • NAID: 10030315934
  • Peer Reviewed
• [Journal Article] Comparison of the efficacy and safety of irbesartan and olmesartan in patients with hypertension (EARTH study) (2012)
  • Author(s): Morii, J., Miura, S., Shiga, Y., Sugihara, M., Arimura, T., Sako, H., Zhang, B., Uehara, Y., Saku, K.
  • Journal Title: Clin Exp Hypertens Volume: 34 Issue: 5 Pages: 342-9
  • DOI: 10.3109/10641963.2012.683912
  • Peer Reviewed
• [Journal Article] Antiatherogenic effects of newly developed apolipoprotein A-I mimetic peptide/phospholipid complexes against aortic plaque burden in Watanabe-heritable hyperlipidemic rabbits. (2011)
  • Author(s): Iwata A, Miura S, Zhang B., Imaizumi, S., Uehara, Y., Shiomi, M., Saku, K.
  • Journal Title: Atherosclerosis Volume: 218 Pages: 300-307
  • Peer Reviewed
• [Presentation] Effects of CNT-01 on the Production of Lipids and Lipoproteins from the Small Intestine in Mice (2015)
  • Author(s): Zhang B, Yamaguchi S, Hirano K
  • Organizer: The 3rd International Symposium on
  • Place of Presentation: Tokyo, JAPAN
  • Year and Date: 2015-03-14
• [Presentation] 日本のタバコ消費の経時変化と心疾患死亡率の関係 (2013)
  • Author(s): 張 波
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] アポA-I模倣ペプチドとリン脂質の複合体（ETC-642）を利用したHDL治療の動脈硬化抑制効果 (2011)
  • Author(s): 張 波、三浦 伸一郎、岩田 敦、今泉 聡、上原 吉就、黒木 政秀、朔 啓二郎
  • Organizer: 第１5回バイオ治療法研究会学術集会
  • Place of Presentation: 福岡
• [Book] 動脈硬化症の新しい診断・治療標的 (2012)
  • Author(s): 谷川宏之，張 波，黒木政秀，朔啓二郎
  • Total Pages: 204
  • Publisher: メディカルレビュー社