Role of serum mass and activity of endothelial lipase in serum high-density lipoprotein cholesterol level in humans

血清质量和内皮脂肪酶活性对人血清高密度脂蛋白胆固醇水平的影响

• 批准号: 21590897
• 负责人: ISHIDA Tatsuro
• 金额: $ 2.91万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590897/
• 关键词: 脂質代謝; 循環器; 血管内皮; リポ蛋白代謝; リパーゼ; 脂質異常症; 動脈硬化; 臨床; 生活習慣病; 高比重リポ蛋白; 臨床検査

High-density lipoprotein cholesterol(HDL-C) has a variety of athero-protective actions. Endothelial lipase(EL) hydrolyzes phospholipids in the HDL particle and promotes its catabolism. However, the role of EL in HDL-C levels and atherosclerosis in humans has not been fully elucidated. In this study, we further investigated the role of plasma concentration and activity of EL in HDL-C levels in human subjects.We have established a novel ELISA system for plasma EL mass by using two monoclonal antibodies against human EL. EL-specific plasma phospholipase activity was measured using a fluorogenic phospholipid as a substrate, after plasma EL protein was immunopricipited using anti-EL antibodies. The plasma EL mass and activity were inversely correlated with plasma HDL-C levels. In addition, the EL mass or activity in patients with cardiovascular diseases was significantly higher than those in patients with cardiovascular diseases. The EL mass or activity was correlated with coronary risk factors including cigarette smoking, high-sensitive CRP, and dyslipidemia.In conclusion, plasma EL mass and activity are determinants of plasma HDL-C levels, and correlated with risks in cardiovascular diseases. Because inhibition of plasma EL activity increased anti-inflammatory HDL particles, EL may represent a novel target for HDL-raising pharmaceutical interventions for patients with low HDL levels.

高密度脂蛋白胆固醇（HDL-C）具有多种抗动脉粥样硬化作用。内皮脂肪酶（EL）水解HDL颗粒中的磷脂并促进其催化。然而，EL在人类HDL-C水平和动脉粥样硬化中的作用尚未完全阐明。本研究进一步探讨了血浆EL浓度和活性对HDL-C水平的影响，并利用两株抗人EL单克隆抗体建立了一种新的血浆EL质量ELISA检测体系。EL特异性血浆磷脂酶活性测定使用荧光磷脂作为底物，血浆EL蛋白免疫沉淀后，使用抗EL抗体。血浆EL质量和活性与血浆HDL-C水平呈负相关。此外，心血管疾病患者的EL质量或活性显著高于心血管疾病患者。EL质量或活性与吸烟、高敏C反应蛋白（hsCRP）、血脂异常等冠心病危险因素相关，提示血浆EL质量和活性是血浆HDL-C水平的决定因素，与心血管疾病的危险性相关。由于血浆EL活性的抑制增加了抗炎HDL颗粒，EL可能代表了HDL升高药物干预低HDL水平患者的新靶点。

项目成果

Endothelial cell-selective adhesion molecule modulates atherosclerosis through plaque angiogenesis and monocyte-endothelial interaction

• DOI: 10.1016/j.mvr.2010.04.005
• 发表时间: 2010-09-01
• 期刊: MICROVASCULAR RESEARCH
• 影响因子: 3.1
• 作者: Inoue, Michihiko;Ishida, Tatsuro;Hirata, Ken-ichi
• 通讯作者: Hirata, Ken-ichi

Endothelial lipase mediates HDL levels in normal and hyperlipidemic rabbits.

• DOI: 10.5551/jat.11148
• 发表时间: 2012
• 期刊: Journal of atherosclerosis and thrombosis
• 影响因子: 4.4
• 作者: 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 K;Hurt-Camejo E;Chen YE;Fan J
• 通讯作者: Fan J

Plasma EL activity is inversely correlated with the HDL-cholesterol level in humans

血浆 EL 活性与人类 HDL 胆固醇水平呈负相关

• 发表时间: 2010
• 作者: Sun L;et al.
• 通讯作者: et al.

HDLの異化の制御のCardiovascular Riskにおける役割を考える

考虑 HDL 分解代谢控制在心血管风险中的作用

• 发表时间: 2009
• 期刊: Progress in Medicine. 6
• 作者: Tojo K;Tsuchiya-Suzuki A;Sekijima Y;Morita H;Sumita N;Ikeda S;石田達郎
• 通讯作者: 石田達郎

Targeted deletion of endothelial lipase increases HDL particles with anti-inflammatory properties both in vitro and in vivo

• DOI: 10.1194/jlr.m008417
• 发表时间: 2011-01-01
• 期刊: JOURNAL OF LIPID RESEARCH
• 影响因子: 6.5
• 作者: Hara, Tetsuya;Ishida, Tatsuro;Hirata, Ken-ichi
• 通讯作者: Hirata, Ken-ichi