Effects of dysfunctional HDL on coronary artery disease

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790852
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: Kobe University
• Principal Investigator: TOH Ryuji 神戸大学, 大学院・医学研究科, 院医学研究科 (50379418)
• Project Period (FY): 2011 – 2012
• Keywords: 高比重リポ蛋白 / HDL機能不全 / 冠動脈疾患 / 動脈硬化 / パラオキソナーゼ / ミエロペルオキシダーゼ / 炎症 / 再狭窄

Research Abstract

High-density lipoprotein cholesterol (HDL-C) is a negative risk factor for CAD. HDL exhibits a variety of anti-atherogenic functions including anti-inflammatory and anti-oxidative as well as promoting reverse cholesterol transport. However, it has been reported that HDL may lose its anti-atherogenic properties and become pro-atherogenic (dysfunctional) under conditions such as inflammation, diabetes, and oxidative stress. In this study, we evaluated HDL function in Japanese patients, and investigated effects of dysfunctional HDL on coronary artery disease (CAD).
1) Granular leukocyte-derived myeloperoxidase (MPO) promotes oxidation of lipoproteins, while paraoxonase 1 (PON1) has antioxidant properties for high-density lipoprotein (HDL). We found that serum MPO/PON1 ratio reflect anti-inflammatory properties of HDL. Furthermore, MPO/PON1 ratio was significantly associated with the prevalence of coronary lesions in Japanese patients.
2) Pitavastatin has a function of increasing plasma HDL-C levels as well as decreasing low-density lipoprotein cholesterol levels. We demonstrated that pitavastatin also enhances cholesterol efflux capacity and antioxidative properties of HDL.

Research Products

• [Journal Article] Pitavastatin increases HDL particles functionally-preserved with cholesterol efflux capacity and anti-oxidative action in dyslipidemia patients (2013)
  • Author(s): Miyamoto-Sasak i M, Yasuda T , Monguchi T, Toh R, Ishida T, Hirata K.
  • Journal Title: J Atheroscler Thromb Volume: (掲載確定)
• [Journal Article] Endothelial lipase modulates pressure overload- induced heart failure through alternative pathway for fatty acid uptake (2013)
  • Author(s): Nakajima H, Ishida T, Satomi-Kobayashi S, Mori K, Hara T, Sasaki N, Yasuda T, Toh R, Tanaka H, Kawai H, Hirata K.
  • Journal Title: Hypertension Volume: 61(5) Pages: 1002-7
• [Journal Article] Expression of endothelial lipase correlates with the size of neointima in a murine model of vascular remodeling (2012)
  • Author(s): Sun L, Ishida T, Okada T, Yasuda T, Hara T, Toh R, Shinohara M, Yamashita T, Rikitake Y, Hirata K
  • Journal Title: Atheroscler Thromb Volume: 19 Pages: 1110-1127
• [Presentation] Trans fatty acids increase inflammatory cytokines in plasma and aorta and decrease fatty acid elongation in LDL receptor knockout mice (2013)
  • Author(s): Hasokawa M, Shinohara M, Yasuda T, Toh R, Ishida T, Hirata K
  • Organizer: 第77回日本循環器学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-17
• [Presentation] Myeloperoxidase and paraoxonase 1 modulate functional quality of HDL and progression of coronary artery lesions (2012)
  • Author(s): Haraguchi Y, Toh R, Ishida T, Monguchi T,Sasaki M, Mori K,Kondo K, Hasokawa M,Nakajima H, Hirata K
  • Organizer: American Heart Association Scientific Sessions 2012
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2012-11-07
• [Presentation] Trans fatty acid is a modulator of serum lipoprotein metabolism and coronary artery disease in Japanese subjects (2012)
  • Author(s): 破磯川 実、篠原 正和、門口 倫子、佐々木 真希、近藤 健介、森 健太、中島 英人、原口 英子、安田 知行、杜 隆嗣、石田 達郎、平田 健一
  • Organizer: 第44回日本動脈硬化学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2012-07-19
• [Presentation] Fasting serum concentration of apolipoprotein B48 is a putative predictor of coronary risk in patients with coronary artery disease (2012)
  • Author(s): 森 健太、石田 達郎、門口 倫子、佐々木 真希、近藤 健介、破磯川 実、中島 英人、原口 英子、杜隆嗣、安田 知行、篠原 正和、西村 邦弘、平田 健一
  • Organizer: 第44回日本動脈硬化学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2012-07-19
• [Presentation] Role of ndothelial lipase in HDL metabolism and atherosclerosis in humans (2011)
  • Author(s): Ishida T, Toh R, Sun L, Yasuda T, Hirata K
  • Organizer: 79th European Atherosclerosis Society Congress
  • Place of Presentation: Gothenburg, Sweden.
  • Year and Date: 2011-06-28