A comprehensive analysis of high density lipoprotein function

• Project/Area Number: 25461085
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kobe University
• Principal Investigator: HIRATA KEN-ICHI 神戸大学, 医学(系)研究科(研究院), 教授 (20283880)
• Co-Investigator(Kenkyū-buntansha): TOH Ryuji 神戸大学, 大学院医学研究科, 特命准教授 (50379418)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 高比重リポ蛋白 / 動脈硬化 / ミエロペルオキシダーゼ / パラオキソナーゼ１ / コレステロール取り込み能 / コレステロール

Outline of Final Research Achievements

Aim: Recent studies suggest that the function of high-density lipoprotein （HDL） modulate and predict the progression of cardiovascular disease in addition to the quantity of HDL. In the present studies, we sought to establish conventional methods to assess functional changes in HDL for clinical use. Results: 1) Myeloperoxidase (MPO) promotes oxidation of lipoproteins, while paraoxonase 1 (PON1) has antioxidant properties for HDL. Serum MPO/PON1 ratio is inversely related with the anti-inflammatory properties and cholesterol efflux capacity of HDL. We demonstrated the clinical utility of serum MPO/PON1 ratio in predicting recurrent coronary lesions after percutaneous coronary intervention (PCI). 2) We established the methods to assess cholesterol uptake capacity of HDL in a sensitive and high-throughput manner without using radioisotope-label and cells. We demonstrated a significant inverse association between requirement of revascularization after PCI and cholesterol uptake capacity.

Research Products

• [Journal Article] Serum Trans-Fatty Acid Concentration Is Elevated in Young Patients With Coronary Artery Disease in Japan (2015)
  • Author(s): Mori K, Ishida T, Yasuda T, Hasokawa M, Monguchi T, Sasaki M, Kondo K, Nakajima H, Shinohara M, Shinke T, Irino Y, Toh R, Nishimura K, Hirata K.
  • Journal Title: Circulation Journal Volume: 79 Issue: 9 Pages: 2017-2025
  • DOI: 10.1253/circj.CJ-14-0750
  • NAID: 130005095322
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] Administration of high dose eicosapentaenoic acid enhances anti-inflammatory properties of high-density lipoprotein in Japanese patients with dyslipidemia (2014)
  • Author(s): Tanaka N, Ishida T, Nagao M, Mori T, Monguchi T, Sasaki M, Mori K, Kondo K, Nakajima H, Honjo T, Irino Y, Toh R, Shinohara M, Hirata K
  • Journal Title: Atherosclerosis Volume: 237 Issue: 2 Pages: 577-583
  • DOI: 10.1016/j.atherosclerosis.2014.10.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Trans-fatty acid promotes thrombus formation in mice by aggravating antithrombogenic endothelial functions via Toll-like receptors. (2014)
  • Author(s): Kondo K, Ishida T, Yasuda T, Nakajima H, Mori K, Tanaka N, Mori T, Monguchi T, Shinohara M, Irino Y, Toh R, Rikitake Y, Kiyomizu K, Tomiyama Y, Yamamoto J, Hirata K.
  • Journal Title: Molecular Nutrition & Food Research Volume: 59 Issue: 4 Pages: 729-740
  • DOI: 10.1002/mnfr.201400537
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Serum myeloperoxidase/paraoxonase 1 ratio as potential indicator of dysfunctional high-density lipoprotein and risk stratification in coronary artery disease. (2014)
  • Author(s): Haraguchi Y1, Toh R2, Hasokawa M1, Nakajima H1, Honjo T1, Otsui K1, Mori K1, Miyamoto-Sasaki M1, Shinohara M1, Nishimura K3, Ishida T1, Hirata KI1
  • Journal Title: Atherosclerosis Volume: 234 Issue: 2 Pages: 288-294
  • DOI: 10.1016/j.atherosclerosis.2014.03.009
  • Peer Reviewed / Open Access
• [Journal Article] Pitavastatin Increases HDL Particles Functionally Preserved with Cholesterol Efflux Capacity and Antioxidative Actions in Dyslipidemic Patients (2013)
  • Author(s): Maki Sasaki-Miyamoto
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 20 Issue: 9 Pages: 708-716
  • DOI: 10.5551/jat.17210
  • NAID: 130004845448
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed
• [Journal Article] Vasospasm of Atherosclerotic Coronary Arteries Precipitates Acute Ischemic Myocardial Damage in Myocardial Infarction-Prone Strain of the Watanabe Heritable Hyperlipidemic Rabbits. (2013)
  • Author(s): Shiomi M, Ishida T, Kobayashi T, Nitta N, Sonoda A, Yamada S, Koike T, Kuniyoshi N, Murata K, Hirata KI, Ito T, Libby P.
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: 33 Issue: 11 Pages: 2518-2523
  • DOI: 10.1161/atvbaha.113.301303
  • Peer Reviewed
• [Presentation] Cholesterol Uptake Capacity, a New Measure for High-Density Lipoprotein Functionality And Its Association with Incident Cardiovascular Events (2016)
  • Author(s): Toshihiko Oshita, Tetsuya Hara, Amane Harada, Katsuhiro Murakami, Maria Kiriyama, Keiko Yoshikawa, Keiko Miwa, Yasuhiro Irino, Kenta Mori, Ryuji Toh, Tatsuro Ishida, Ken-ichi Hirata
  • Organizer: 第80回 日本循環器学会 学術集会
  • Place of Presentation: 仙台 日本
  • Year and Date: 2016-03-18
• [Presentation] Endothelial Lipase Regulates Plasma HDL-C Concentration without Affecting Cholesterol Uptake Capacity of HDL Particle in Patients with Coronary Artery Disease. (2016)
  • Author(s): Amane Harada, Ryuji Toh, Katsuhiro Murakami, Maria Kiriyama, Keiko Yoshikawa, Takuya Kubo, Keiko Miwa, Yasuhiro Irino, Kenta Mori, Nobuaki Tanaka, Tatsuro Ishida, Ken-ichi Hirata
  • Organizer: 第80回 日本循環器学会 学術集会
  • Place of Presentation: 仙台 日本
  • Year and Date: 2016-03-18
• [Presentation] Serum Myeloperoxidase/Paraoxonase 1 Ratio Predicts Recurrent Coronary Artery Disease (2015)
  • Author(s): Tsuda S, Toh R, Mori K, Nagao M, Tanaka N, Mori T, Monguchi T, Nakajima H, Honjo T, Shinohara M, Nishimura K, Ishida T, Hirata K
  • Organizer: 第47回 日本動脈硬化学会総会学術集会
  • Place of Presentation: 仙台 日本
  • Year and Date: 2015-07-09
• [Presentation] 冠動脈疾患二次予防における予測因子としての血清ミエロペルオキシダーゼ/パラオキソナーゼ1比の有用性についての検討 (2015)
  • Author(s): Tsuda S, Toh R, Mori K, Nagao M, Tanaka N, Mori T, Monguchi T, Nakajima H, Honjo T, Shinohara M, Nishimura K, Ishida T, Hirata K
  • Organizer: 第15回日本NO学会
  • Place of Presentation: 大阪 日本
  • Year and Date: 2015-06-26
• [Presentation] Serum myeloperoxidase/paraoxonase 1 ration predicts recurrent coronary artery disease (2015)
  • Author(s): Tsuda S, Toh R, Mori K, Nagao M, Tanaka N, Mori T, Monguchi T, Nakajima H, Honjo T, Shinohara M, Nishimura K, Ishida T, Hirata K
  • Organizer: ATVB PVD 2015 Scientific Sessions
  • Place of Presentation: サンフランシスコ 米国
  • Year and Date: 2015-05-07
  • Int'l Joint Research
• [Presentation] Impact of Serum Myeloperoxidase/Paraoxonase 1 Ratio as a Predictive Marker of for Secondary Prevention of Coronary Artery Disease (2015)
  • Author(s): Tsuda S, Toh R, Mori K, Nagao M, Tanaka N, Mori T, Monguchi T, Nakajima H, Honjo T, Shinohara M, Nishimura K, Ishida T, Hirata K
  • Organizer: 第79回 日本循環器学会 学術集会
  • Place of Presentation: 大阪 日本
  • Year and Date: 2015-04-24
• [Presentation] Oral administration of eicosapentaenoic acid ameliorates anti-inflammatory functions of high-density lipoprotein in dyslipidemic patients (2014)
  • Author(s): Nobuaki Tanaka, Tatsuro Ishida, Manabu Nagao, Takeshige Mori, Tomoko Monguchi, Maki Sasaki, Kenta Mori, Kensuke Kondo, Hideto Nakajima, Tomoyuki Honjo, Ryuji Toh, Ken-ichi Hirata
  • Organizer: American Heart Association Scientific Sessions 2014
  • Place of Presentation: シカゴ アメリカ
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Eicosapentaenoic acid improves anti-inflammatory functions of high-density lipoprotein in dyslipidemic patients (2014)
  • Author(s): Nobuaki Tanaka, Tatsuro Ishida, Manabu Nagao, Takeshige Mori, Tomoko Monguchi, Maki Sasaki, Kenta Mori, Kensuke Kondo, Hideto Nakajima, Tomoyuki Honjo, Ryuji Toh, Ken-ichi Hirata
  • Organizer: 第46回日本動脈硬化学会総会
  • Place of Presentation: 東京 日本
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] 高比重リポ蛋白による心筋細胞保護作用の検討 (2014)
  • Author(s): 中島英人、石田達郎、平田健一
  • Organizer: 第46回日本動脈硬化学会総会
  • Place of Presentation: 東京 日本
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] Impact of endothelial lipase on the low HDL-cholesterol level under inflammatory conditions (2014)
  • Author(s): Tatsuro Ishida, Ken-ichi Hirata
  • Organizer: 第46回日本動脈硬化学会総会
  • Place of Presentation: 東京 日本
  • Year and Date: 2014-07-10 – 2014-07-11
  • Invited
• [Presentation] Inflammation-Activated Angptl3-Endothelial Lipase System Regulates Serum HDL-C Levels in Acute Coronary Syndrome (2014)
  • Author(s): Kenta Mori, Tatsuro Ishida, Kazuya miyashita, Noriaki Kinoshita, Hideto Nakajima, Tomoyuki Yasuda, Ryuji Toh, Masahito Kawata, Susumu Sakamoto, Katsuyuki Nakajima, Ken-ichi Hirata.
  • Organizer: 第46回日本動脈硬化学会総会
  • Place of Presentation: 東京 日本
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] 機能不全HDLの簡便な臨床評価法としての血清MPO/PON1比測定の有用性 (2014)
  • Author(s): 杜 隆嗣、石田 達郎、西村 邦宏、平田 健一
  • Organizer: 第111回 日本内科学会総会
  • Place of Presentation: 東京 日本
  • Year and Date: 2014-04-11 – 2014-04-13
• [Presentation] Role of endothelial lipase in high-density lipoprotein (HDL) metabolism in humans. (2013)
  • Author(s): Tatsuro Ishida
  • Organizer: The 81st Congress of the European Atherosclerosis Society
  • Place of Presentation: Lyon, France
• [Presentation] Increases of Serum Mass of Endothelial Lipase Impact Plasma High-Density Lipoprotein-Cholesterol Concentrations in Acute Myocardial Infarction. (2013)
  • Author(s): Kenta Mori
  • Organizer: The 81st Congress of the European Atherosclerosis Society
  • Place of Presentation: Lyon, France
• [Presentation] Impact of oral eicosapentaenoic acid therapy on High-Density Lipoprotein function in patients with high risk of atherosclerosis.
  • Author(s): Nobuaki Tanaka
  • Organizer: The 78th Annual Scientific Meeting of the Japanese Circulation Society.
  • Place of Presentation: Tokyo, Japan
• [Presentation] Effect of cholesteryl ester transfer protein inhibitor on anti-inflammatory properties of high-density lipoproteins.
  • Author(s): Kenta Mori
  • Organizer: The 78th Annual Scientific Meeting of the Japanese Circulation Society.
  • Place of Presentation: Tokyo, Japan
• [Presentation] 機能不全HDLマーカーとしての血清MPO/PON1比の有用性
  • Author(s): 杜 隆嗣
  • Organizer: 第43回日本心脈管作動物質学会総会
  • Place of Presentation: 神戸 日本
• [Book] HDLコレステロール (2014)
  • Author(s): 杜 隆嗣、平田 健一
  • Total Pages: 9
  • Publisher: 血管医学
• [Book] 脂質代謝、動脈硬化における機能と臨床的意義 血管内皮リパーゼの炎症と血清HDL代謝における役割 (2013)
  • Author(s): 石田 達郎、平田 健一
  • Total Pages: 10
  • Publisher: The Lipid
• [Book] 【脂質異常症-基礎・臨床研究の最新知見-】 脂質異常症による粥状硬化発症進展機序 (2013)
  • Author(s): 石田 達郎、平田 健一
  • Total Pages: 8
  • Publisher: 日本臨床