Analysis of HDL dysfunction induced by oxidized phospholipids in atherosclerosis.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590558
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Juntendo University
• Principal Investigator: MIIDA Takashi Juntendo University, 医学部, 教授 (80260545)
• Co-Investigator(Kenkyū-buntansha): OKADA Masahiko 新潟大学, 医歯学系, 教授 (30018915)
• Research Collaborator: HIRAYAMA Satoshi 順天堂大学, 医学部, 准教授 ; CHIBA Hitoshi 北海道大学, 大学院・保健科学研究院, 教授 (70197622)
• Project Period (FY): 2008 – 2010
• Keywords: 慢性透析患者 / リン脂質 / 酸化ストレス / HDL / 動脈硬化

Research Abstract

Oxidized LDL accumulates in macrophages, while HDL prevents the development of atherosclerosis. This study aimed at examining the relationship between oxidized phospholipids (PL) and impaired HDL function. We collected blood samples from hemodialysis (HD) patients, who have increased oxidative stress and high susceptibility to atherosclerosis. In the HD patients, serum PL concentration was low, but oxidized PL concentration and PL transfer activity increased significantly. In these patients, LCAT-dependent maturation of prebeta1-HDL, small HDL particles, was impaired. In summary, it is suggested that oxidized PL might be transferred from LDL to HDL, and cause impairment of HDL maturation.

Research Products

• [Journal Article] Profiles of inflammatory markers and lipoprotein subclasses in patients undergoing continuous ambulatory peritoneal dialysis. (2010)
  • Author(s): Kon M, Hirayama S, Horiuchi Y, Ueno T, Idei M, Fueki Y, Seino U, Goto S, Maruyama H, Iino H, Fukushima Y, Ohmura H, Hirowatari Y, Miida T
  • Journal Title: Clin Chim Acta 411 Pages: 1723-1727
  • Peer Reviewed
• [Journal Article] Impacts of angiopoietin-like proteins on lipoprotein metabolism and cardiovascular events. (2010)
  • Author(s): Miida T, Hirayama S
  • Journal Title: Curr Opin Lipidol 21 Pages: 70-75
  • Peer Reviewed
• [Journal Article] Statin therapy reduces inflammatory markers in hypercholesterolemic patients who have high baseline levels. (2010)
  • Author(s): Horiuchi Y, Hirayama S, Seino U, Kon K, Ueno T, Ohmura H, Hanyu O, Tsuda T, Miida T
  • Journal Title: J Atheroscler Thromb 17 Pages: 722-729
  • Peer Reviewed
• [Journal Article] Single administration of α-glucosidase inhibitors on endothelial function and incretin secretion in diabetic patients with coronary artery disease. -Juntendo University Trial : effects of miglitol on endothelial vascular reactivity in type 2 diabetic patients with coronary heart disease (2010)
  • Author(s): Hiki M, Shimada K, Kiyanagi T, Fukao K, Hirose K, Ohsaka H, Fukushima Y, Kume A, Matsumori R, Sumiyoshi K, Miyazaki T, Ohmura H, Kurata T, Miida T, Daida H
  • Journal Title: (J-MACH)- Circ J Vol.74,No.7 Pages: 1471-1478
  • Peer Reviewed
• [Journal Article] Circadian change of serum concentration of small dense LDL-cholesterol in type 2 diabetic patients. (2010)
  • Author(s): Hirayama S, Soda S, Ito Y, Matsui H, Ueno T, Fukushima Y, Ohmura H, Hanyu O, Aizawa Y, Miida T
  • Journal Title: Clin Chim Acta Vol.411,No.3-4 Pages: 253-257
  • Peer Reviewed
• [Journal Article] Altered metabolisms of mediators controlling vascular function and enhanced oxidative stress in asymptomatic children with congenital portosystemic venous shunt. (2010)
  • Author(s): Nagasaka H, Okano Y, Aizawa M, Miida T, Yorifuji T, Tajima, G Sakura N, Takatani T, Sanayama Y, Sugamoto K, Mayumi M, Kobayashi K, Hirano K, Takayanagi M, Tsukahara H
  • Journal Title: Metabolism Vol.59,No.1 Pages: 107-113
  • Peer Reviewed
• [Journal Article] Lipoprotein profile in children with two common cholesteryl ester transfer protein gene mutations, D442G and I14A, during the first year of life (2009)
  • Author(s): Nagasaka H, Yorifuji T, Momoi T, Yorifuji J, Hirano K, Ota A, Takatani T, Tsukahara H, Takayanagi M, Kobayashi K, Chiba H, Sato Y, Miida T
  • Journal Title: Clin Chim Acta 406 Pages: 52-56
  • Peer Reviewed
• [Journal Article] Preβ1-HDL is elevated in the fasting state, but markedly reduced postprandially in poorly controlled type 2 diabetic patients. (2009)
  • Author(s): Hirayama S, Ito T, Miyazaki O, Kamimura T, Hanyu O, Seino U, Ito S, Aizawa Y, Miida T
  • Journal Title: Clin Chim Acta 401 Pages: 57-62
  • Peer Reviewed
• [Journal Article] 慢性透析患者における脂質プロフィールと炎症マーカーの検討 (2009)
  • Author(s): 笛木百合子、石井雄士、桜井信行、飯野則昭、後藤眞、丸山弘樹、岡田正彦、昆美香、堀内裕紀、出居真由美、三井田孝
  • Journal Title: 生物試料分析 32 Pages: 328-333
  • Peer Reviewed
• [Journal Article] Measurement of cholesterol levels of major serum lipoprotein classes in hemodialysis patients by anion-exchange chromatography. (2008)
  • Author(s): Hirowatari Y, Yoshida H, Fueki Y, Ito M, Ogura Y, Sakurai N, Miida T
  • Journal Title: Ann Clin Biochem 45 Pages: 571-574
  • Peer Reviewed
• [Journal Article] Probucol markedly reduces HDL phospholipids and elevated preβ1-HDL without delayed conversion into α-migrating HDL : putative role of angiopoietin-like protein 3 in probucol-induced HDL remodeling. (2008)
  • Author(s): Miida T, Seino U, Miyazaki O, Hanyu O, Hirayama S, Saito T, Ishikawa Y, Akamatsu S, Nakano T, Nakajima K, Okazaki M, Okada M
  • Journal Title: Atherosclerosis 200 Pages: 329-335
  • Peer Reviewed
• [Journal Article] Experimental evidence that phenylalanine is strongly associated to oxidative stress in adolescents and adults with phenylketonuria.
  • Author(s): Sanayama Y, Nagasaka H, Takayanagi M, Ohura T, Sakamoto O, Ito T, Ishige-Wada M, Usui H, Yoshino M, Ohtake A, Yorifuji T, Tsukahara H, Hirayama S, Miida T, Fukui M, Okano Y
  • Journal Title: Mol Genet Metab (in press)
  • Peer Reviewed
• [Journal Article] Small dense LDL cholesterol is a robust therapeutic marker of statin treatment in patients with acute coronary syndrome and metabolic syndrome.
  • Author(s): Fukushima Y, Hirayama S, Ueno T, Dohi T, Miyazaki T, Ohmura H, Mokuno H, Miyauchi K, Miida T, Daida H
  • Journal Title: Clin Chim Acta (in press)
  • Peer Reviewed
• [Presentation] Oxysterols levels in plasma and the correlation to the age. (2010)
  • Author(s): Hasegawa E, Nakagawa S, Hirayama S, Miida T, Sanayama Y, Nagasaka H, Yamato S.
  • Organizer: The 12th Asian-Pacific Congress of Clinical Biochemistry
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20101003-20101007
• [Presentation] Measurement of surrogate markers related to cholesterol metabolism in plasma of patients with ezetimibe administration. (2010)
  • Author(s): Kamimura Y, Nakagawa S, Hirayama S, Miida T, Yamato S
  • Organizer: The 12th Asian-Pacific Congress of Clinical Biochemistry
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20101003-20101007
• [Presentation] Determination of isoprenoids in human plasma by LC-MS/MS. (2010)
  • Author(s): Kuwabara N, Nakagawa S, Hirayama S, Miida T, Yamato S
  • Organizer: The 12th Asian-Pacific Congress of Clinical Biochemistry
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20101003-20101007
• [Presentation] Cholesterol sulfate regulation of profilaggrin expression : Studies involving siRNA for SULT2B1b and ROR alpha in primary cultures of normal human epidermal keratinocytes. (2010)
  • Author(s): Hanyu O, Fuda H, Higashi Y, Endo M, Nakae H, Kohjitani A, Miida T, Aizawa Y, Strott CA
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: Kyoto
  • Year and Date: 20100326-20100330
• [Presentation] Preβ1-HDL : A potential marker for HDL function. (2008)
  • Author(s): Miida T.
  • Organizer: Annual Meeting of American Association for Clinical Chemistry (AACC)
  • Place of Presentation: Washington DC, U.S.A.
  • Year and Date: 20080720-20080731
• [Presentation] Preβ1-HDL : A potential marker for HDL function. (2008)
  • Author(s): Miida T.
  • Organizer: Annual Meeting of American Association for Clinical Chemistry
  • Place of Presentation: Washington DC, U.S.A.
  • Year and Date: 2008-07-29
• [Book] The HDL Handbook -Biological Functions and Clinical Implications(Komoda T, Ed)(Chapter 12 : Preβ1-HDL : A native lipid-poor HDL, and its potential as a new marker for HDL metabolism 査読有). (2010)
  • Author(s): Miida T, Hirayama S
  • Total Pages: 243-259
  • Publisher: Academic Press
• [Book] コレステロール-基礎から臨床へ-(寺本民生編)(コレステロール逆転送系の発見) (2009)
  • Author(s): 平山哲、三井田孝
  • Total Pages: 236-241
  • Publisher: ライフサイエンス
• [Remarks] ホームページ等
  • URL: http://www.juntendo.ac.jp/med/labo/rinsyo_byori.html