Effect of altered expression of endothelial lipase on plasma lipids and atherosclerosis in rabbits

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790854
• 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: SUN Li 神戸大学, 大学院・医学研究科, 医学研究員 (10547508)
• Co-Investigator(Renkei-kenkyūsha): ISHIDA Tatsuro 神戸大学, 医学部附属病院, 准教授 (00379413) ; YASUDA Tomoyuki 神戸大学, 医学部附属病院, 助教 (20457047)
• Project Period (FY): 2011 – 2012
• Keywords: 高比重リポ蛋白 / 炎症 / 脂質代謝 / 血管内皮 / リパーゼ / 動脈硬化 / 家兎

Research Abstract

Endothelial lipase (EL) regulates circulating high-density lipoprotein-cholesterol (HDL-C) levels. There is a discrepancy of EL effect in lipid profiles between mise and humans. Therefore, we investigated the effect of altered EL expression on lipid profile and HDL anti-atherogenic properties in rabbits. Adenovirus encoding human EL (AdhEL) was injected into Japanese white rabbits, which induced hEL overexpression. Consequently, serum HDL-C levels were significantly decreased, while LDL-C levels were not affected. Lipoprotein fractions isolated from humans, rabbits and mice were treated with the EL-rich medium, and measured free fatty acids liberated from the lipoprotein substrates. The hEL hydrolyzed HDL from all three species, while it hydrolyzed mouse LDL much greater than rabbit- and human-LDL. Serum paraoxonase activity, a major component of HDL anti-oxidant properties, significantly reducedin EL-overexpressing rabbits, whereas serum cholesterol efflux capacity did not change despite of the reduced HDL levels. In conclusion, Human EL reduced HDL-C and HDL anti-oxidative property in rabbits. Considering that lipid profile of rabbits resembles that of humans, alteration of EL expression or activity may improve HDLlevels and anti-oxidant properties without affecting LDL-C levels in humans.

Research Products

• [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] Fasting serum concentration of apolipoprotein B48 represents residual risks in patients with new-onset and chronic coronary artery disease (2013)
  • Author(s): Mori K, Ishida T, Yasuda T, Monguchi T, Sasaki M, Kondo K, Hasokawa M, Nakajima H, Haraguchi Y, Sun L, Shinohara M, Toh R, Nishimura K, Hirata K
  • Journal Title: Clin Chim Acta Volume: 421C Pages: 51-56
  • DOI: DOI:10.1016/j.cca.2013.02.005
• [Journal Article] Enzyme-linked immunosorbent assay system for human endothelial lipase (2012)
  • Author(s): Ishida T, Miyashita K, Shimizu M, Kinoshita N, Mori K, Sun L, Yasuda T, Imamura S, Nakajima K, Stanhope KL, Havel PJ, Hirata K
  • Journal Title: Clin Chem Volume: 58(12) Pages: 1656-64
  • DOI: DOI:10.1373/clinchem.2012.187914
• [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: J Atheroscler Thromb Volume: 19(12) Pages: 1110-27
• [Journal Article] Identification of biomarkers of stent restenosis with serum metabolomic profiling using gas chromatography/mass spectrometry (2012)
  • Author(s): Hasokawa M, Shinohara M, Tsugawa H, Bamba T, Fukusaki E, Nishiumi S, Nishimura K, Yoshida M, Ishida T, Hirata K
  • Journal Title: Circ J Volume: 76(8) Pages: 1864-73
• [Journal Article] Endothelial lipase mediates HDL levels in normal and hyperlipidemic rabbits (2012)
  • Author(s): Zhang J, Yu Y, Nakamura K, Koike T, Waqar AB, Zhang X, Liu E, Nishijima K, Kitajima S, Shiomi M, Qi Z, Yu J, Graham MJ, Crooke RM, Ishida T, Hirata KI, Hurt-Camejo E, Chen YE, Fan J
  • Journal Title: J Atheroscler Thromb Volume: 19(3) Pages: 213-26
• [Journal Article] Pitavastatin increases HDL particles functionally preserved with cholesterol efflux capacity and anti-oxidative action in dyslipidemia patients
  • Author(s): Sasaki-Miyamoto M, Yasuda T, Monguchi T, Nakajima H, Mori K, Toh R, Ishida T, Hirata K
  • Journal Title: J Atheroscler Thromb Volume: 掲載確定
• [Presentation] Effect of overexpression of endothelial lipase on HDL metabolism and HDL anti-atherogenic properties in rabbits (2013)
  • Author(s): Yasuda T, Ishida T, Mori K, Hirata K
  • Organizer: 第77回日本循環器学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-15
• [Presentation] Generation of a high-sensitive and reliable ELISA system that can quantitatively measure human serum mass of endothelial lipase (2012)
  • Author(s): 宮下かずや、石田達郎、安田知行、孫麗、木下憲明、中嶋克行、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: 2012-07-15
• [Presentation] 血管内皮リパーゼ特異的酵素活性と血清HDLコレステロールおよび冠動脈疾患との関連性の検討 (2012)
  • Author(s): 孫麗、石田達郎、森健太、安田知行、中島英人、破磯川実、原口英子、佐々木真希、近藤健介、平田健一
  • Organizer: 第12回日本NO学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2012-06-29
• [Presentation] Plasma mass and activity of endothelial lipase are associated with coronary risk factors in humans (2012)
  • Author(s): Ishida T, Mori K, Sun L, Yasuda T, Hirata K
  • Organizer: The XVI International Symposium on Atherosclerosis (ISA2012)
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2012-03-27
• [Presentation] 糖尿病性動脈硬化における脂質異常の関与 (2011)
  • Author(s): 石田達郎
  • Organizer: 第26回日本糖尿病合併症学会総会
  • Place of Presentation: 大宮
  • Year and Date: 2011-10-14
• [Presentation] Role of endothelial 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