Effect of high-density lipoprotein on cardiac function

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590783
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kobe University
• Principal Investigator: KAWAI Hiroya 神戸大学, 大学院・医学研究科, 教授 (20346266)
• Co-Investigator(Kenkyū-buntansha): TOH Ryuji 神戸大学, 医学研究科, 准教授 (50379418)
• Co-Investigator(Renkei-kenkyūsha): ISHIDA Tatsuro 神戸大学, 医学部附属病院, 准教授 (00379413)
• Project Period (FY): 2010 – 2012
• Keywords: 心不全 / 高比重リポ蛋白 / 炎症 / 脂質代謝 / 血管内皮 / リパーゼ

Research Abstract

Under normal conditions, the heart utilizes nearly 70% of itsenergy through the oxidation of fatty acids (FA). FA are supplied to the heart from the hydrolysis of triglyceride-rich lipoproteins by triglyceride lipase members. Lipoprotein lipase(LPL) has been considered as the only enzyme capable of this function. Endothelial lipase (EL) exhibits primarily phospholipase activity against high-density lipoproteins, but to a lesser extent, triglyceridelipase activity. In this study, we evaluated the role of cardiac EL under conditions of increased energy needs. Pressure overload-induced cardiac hypertrophy was generated in C57Bl/6 mice by ascending aortic constriction, and EL expression in the hypertrophied hearts was evaluated. Cardiac EL expression was elevated in the early stage of cardiac hypertrophy. Complementary cell culture experiments using rat neonatal cardiomyocytes revealed that inflammatory cytokines and lipopolysaccharides increased EL expression in cardiomyocytes, while LPL was decreased by the inflammatory stimuli. In addition, the inflammatory stimuli-induced EL expression was inversely correlated with the expression of carnitine palmitoyltransferase Ib, which is a key enzyme involved in the regulation of FA oxidation and utilization. Furthermore, cardiac EL expression was associated with its function. EL may be an alternative pathway to supply FA to the heart and regulate cardiac function. This function was likely relevant particularly under inflammatory conditions where LPL is downregulated.

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
  • DOI: DOI:10.1161/HYPERTENSIONAHA.111.201608.
  • Peer Reviewed
• [Presentation] Endothelial Lipase would be a molecular target for HDL-raising therapy (2013)
  • Author(s): Tatsuro Ishida
  • Organizer: 2013 WINPTECH
  • Place of Presentation: Kobe
  • Year and Date: 2013-02-19
• [Presentation] Endothelial lipase in the heart modulates pressure overload-induced heart failure through fatty acid utilization. (2012)
  • Author(s): Hideto Nakajima, Tatsuro Ishida, Michiko Monguchi, Maki Sasaki, KensukeKondo, Kenta Mori, Minoru Hasokawa, Yoko Haraguchi, Tomoyuki Yasuda, Ryuji Toh, Seimi Kobayashi, Ken-ichi Hirata
  • Organizer: American Heart Association Scientific Sessions 2012
  • Place of Presentation: Los Angeles, CA, USA.
  • Year and Date: 2012-11-07
• [Presentation] Cardiac endothelial lipase expression is augmented in the early stage of heart failure (2012)
  • Author(s): Hideto Nakajima, Tatsuro Ishida, Maki Sasaki, Kensuke Kondo, Kenta Mori, Minoru Hasokawa, Yoko Haraguchi, Tomoyuki Yasuda, Seimi Kobayashi, Ken-ichi Hirata.
  • Organizer: The XVI International Symposium on Atherosclerosis (ISA2012)
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2012-03-27
• [Presentation] Cardiac endothelial lipase expression is augmented in a murine model of heart failure (2012)
  • Author(s): Hideto Nakajima, Tatsuro Ishida, Monguchi Tomoko, Maki Sasaki, Kensuke Kondo, Kenta Mori, Minoru Hasokawa, Yoko Haraguchi, Sun Li, Tomoyuki Yasuda, Shinohara Masakazu, Toh Ryuji, Seimi Kobayashi, Ken-ichi Hirata
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2012-03-17
• [Presentation] Increased expression of endothelial lipase in a murine model of heart failure. (2011)
  • Author(s): Hideto Nakajima, Tatsuro Ishida, Kensuke Kondo, Kenta Mori, Maki Sasaki, Minoru Hasokawa, Yoko Haraguchi, Tomoyuki Yasuda, Masakazu Shinohara, Seimi Kobayashi, Ken-ichi Hirata
  • Organizer: 第43回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2011-07-16