内皮脂肪酶作为冠心病治疗靶点的研究进展

doi:10.16352/j.issn.1001-6325.2023.09.1443

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (9): 1443-1447.doi: 10.16352/j.issn.1001-6325.2023.09.1443

内皮脂肪酶作为冠心病治疗靶点的研究进展

宋星明, 哈力沙·艾日肯江, 迪丽胡玛尔·阿布来提, 高颖^*

新疆医科大学第一附属医院综合内三科, 新疆乌鲁木齐 830054

收稿日期:2022-08-29 修回日期:2023-02-22 出版日期:2023-09-05 发布日期:2023-09-01
通讯作者: ^*sunflowergaoying@163.com
基金资助:
国家自然科学基金(81660040)

Research progress of endothelial lipase as a therapeutic target for coronary heart disease

SONG Xingming, Harisa·ERKENJIAN, Dilihumal·ABLAITI, GAO Ying^*

The Third Department of General Internal Medicine, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China

Received:2022-08-29 Revised:2023-02-22 Online:2023-09-05 Published:2023-09-01
Contact: ^*sunflowergaoying@163.com

摘要/Abstract

摘要： 内皮脂肪酶(EL)主要由血管内皮细胞生成,负责调控肝脏脂质代谢及肠道脂质吸收。在炎性状态下EL可促进巨噬细胞及血小板在受损血管内皮黏附、聚集;EL还可促进受损血管内皮细胞增殖,抑制EL的过表达可减轻动脉粥样硬化病变程度。但在急性冠脉病变及氧化应激反应时EL却能增强高密度脂蛋白胆固醇抗氧化能力减轻炎性反应对血管内皮损伤,增强受损心肌细胞能量代谢能力抑制受损心肌细胞凋亡。EL抑制剂作为血脂代谢紊乱、动脉粥样硬化疾病新型治疗用药还需更广泛药物临床试验明确其真实临床疗效、安全性及具体临床适用场景。

关键词: 内皮脂肪酶, 脂代谢, 炎性反应, 动脉粥样硬化, 冠心病(CHD)

Abstract: Endothelial lipase(EL) is mainly generated by vascular endothelial cells and is responsible for regulating liver lipid metabolism and intestinal lipid absorption. In the inflammatory state, EL can also promote the adhesion and aggregation of macrophages and platelets in the damaged vascular endothelium. EL can also promote the proliferation of damaged vascular endothelial cells, and inhibit the over-expression of EL can reduce the degree of atherosclerosis. However, in acute coronary artery disease and oxidative stress reaction, EL can enhance the antioxidant capacity of high-density lipoprotein cholesterol, reduce the damage of inflammatory reaction to vascular endothelium, enhance the energy metabolism of damaged cardiomyocytes and inhibit apoptosis of damaged cardiomyocytes. As a new therapeutic drug for dyslipidemia and atherosclerosis, endothelial lipase inhibitor needs more extensive clinical trials to clarify its true clinical efficacy, safety and specific clinical application scenarios.

Key words: endothelial lipase, lipid metabolism, inflammatory reaction, atherosclerosis, coronary heart disease (CHD)

中图分类号:

R816.95

宋星明, 哈力沙·艾日肯江, 迪丽胡玛尔·阿布来提, 高颖. 内皮脂肪酶作为冠心病治疗靶点的研究进展[J]. 基础医学与临床, 2023, 43(9): 1443-1447.

SONG Xingming, Harisa·ERKENJIAN, Dilihumal·ABLAITI, GAO Ying. Research progress of endothelial lipase as a therapeutic target for coronary heart disease[J]. Basic & Clinical Medicine, 2023, 43(9): 1443-1447.

0
/ / 推荐

导出引用管理器 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

链接本文: http://journal11.magtechjournal.com/Jwk_jcyxylc/CN/10.16352/j.issn.1001-6325.2023.09.1443

http://journal11.magtechjournal.com/Jwk_jcyxylc/CN/Y2023/V43/I9/1443

参考文献

[1]Jaye M,Lynch KJ,Krawiec J, et al.A novel endothelial-derived lipase that modulates HDL metabolism[J].Nat Genet,1999,2:424-428.
[2]Liu C,Dhindsa D,Almuwaqqat Z, et al.Association between high-density lipoprotein cholesterol levels and adverse cardiovascular outcomes in high-risk populations[J].JAMA Cardiol,2022,7:672-680.
[3]Yang S,Yin RX,Miao L, et al.LIPG SNPs, their haplotypes and gene-environment interactions on serum lipid levels[J].Lipids Health Dis,2019,18:10.doi:10.1186/s12944-018-0942-y.
[4]Nagao M,Miyashita K,Mori K, et al.Serum concentration of full-length-and carboxy-terminal fragments of endothelial lipase predicts future cardiovascular risks in patients with coronary artery disease[J].J Clin Lipidol,2019,13:839-846.
[5]其布热,周红,董莉.内皮酯酶基因多态性与冠心病的关系研究[J].临床和实验医学杂志,2019,18:699-703.
[6]Schilcher I,Kern S,Hrzenjak A, et al.Impact of endothelial lipase on cholesterol efflux capacity of serum and high-density lipoprotein[J].Sci Rep,2017,7:12485.doi:10.1038/s41598-017-12882-7.
[7]Khetarpal SA,Vitali C,Levin MG, et al.Endothelial lipase mediates efficient lipolysis of triglyceride-rich lipoproteins[J].PLoS Genet,2021,17:e1009802.doi:10.1371/journal.pgen.1009802.
[8]Wu L,Soundarapandian MM,Castoreno AB, et al.LDL-cholesterol reduction by angptl3 inhibition in mice is dependent on endothelial lipase[J].Circ Res,2020,127:1112-1114.
[9]Wang C,Nishijima K,Kitajima S, et al.Increased hepatic expression of endothelial lipase inhibits cholesterol diet-induced hypercholesterolemia and atherosclerosis in transgenic rabbits[J].Arterioscler Thromb Vasc Biol,2017,37:1282-1289.
[10]Wu YE,Ma L,Zhang H, et al.Significant association between the endothelial lipase gene 584C/T polymorphism and coronary artery disease risk[J].Biosci Rep,2020,40.doi:10.1042/BSR20200027.
[11]Schilcher I,Stadler JT,Lechleitner M, et al.Endothelial lipase modulates paraoxonase 1 content and arylesterase activity of HDL[J].Int J Mol Sci,2021,22.doi:10.3390/ijms22020719.
[12]陈永宏,杨松,周建中.阿托伐他汀减轻肾性高血压大鼠血管重构[J].基础医学与临床,2010,30:383-388.
[13]Trimarco V,Izzo R,Morisco C, et al.High HDL(high-density lipoprotein) cholesterol increases cardiovascular risk in hypertensive patients[J].Hypertension,2022,79:2355-2363.
[14]Yue X Wu M,Jiang H, et al.Endothelial lipase is upregulated by interleukin-6 partly via the p38 MAPK and p65 NF-κB signaling pathways[J].Mole Med Reports,2016,14: 1979-1985.
[15]Dalan AB,Toptaş B,Buǧra Z, et al.The effects of endothelial lipase gene (LIPG) variants on inflammation marker levels and atherosclerosis development[J].Mol Biol Rep,2013,40:5143-5149.
[16]Cadenas C,Vosbeck S,Edlund K, et al.LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer[J].Int J Cancer,2019,145:901-915.
[17]Nakajima H,Ishida T,Satomi-Kobayashi S, et al.Endothelial lipase modulates pressure overload-induced heart failure through alternative pathway for fatty acid uptake[J].Hypertension,2013,61:1002-1007.
[18]Schilcher I,Ledinski G,Radulović S, et al.Endothelial lipase increases antioxidative capacity of high-density lipoprotein[J].Biochim Biophys Acta Mol Cell Biol Lipids,2019,1864:1363-1374.
[19]Wan A,Rodrigues B.Endothelial cell-cardiomyocyte crosstalk in diabetic cardiomyopathy[J].Cardiovasc Res,2016,111:172-183.
[20]Yan H,Niimi M,Wang C, et al.Endothelial lipase exerts its anti-atherogenic effect through increased catabolism of β-VLDLs[J].J Atheroscler Thromb,2021,28:157-168.
[21]Kobayashi J.Which is the Best predictor for the develop-ment of atherosclerosis among circulating lipoprotein lipase, hepatic lipase, and endothelial lipase?[J].J Atheroscler Thromb,2019,26:758-759.
[22]Yu X,Lu J,Li J, et al.Serum triglyceride lipase concentrations are independent risk factors for coronary artery disease and in-stent restenosis[J].J Atheroscler Thromb,2019,26:762-774.
[23]Tora G,Kim SH,Pi Z, et al.Identification of reversible small molecule inhibitors of endothelial lipase (EL) that demonstrate HDL-C increase in vivo[J].J Med Chem,2020,63:1660-1670.
[24]Johnson JA,Tora G,Pi Z, et al.Sulfonylated benzothia-zoles as inhibitors of endothelial lipase[J].ACS Med Chem Lett,2018,9:1263-1268.
[25]Ruff CT,Koren MJ,Grimsby J, et al.LEGACY: phase 2a trial to evaluate the safety, pharmacokinetics, and pharmacodynamic effects of the anti-EL(endothelial lipase) antibody MEDI5884 in patients with stable coronary artery disease[J].Arterioscler Thromb Vasc Biol,2021,41:3005-3014.
[26]Meng W,Adam LP,Behnia K, et al.Benzothiazole-based compounds as potent endothelial lipase inhibitors[J].Bioorg Med Chem Lett,2019,29:126673.doi:10.1016/j.bmcl.2019.126673.

内皮脂肪酶作为冠心病治疗靶点的研究进展

Research progress of endothelial lipase as a therapeutic target for coronary heart disease

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	梁辉勇, 韦秋慧, 丁亚, 彭小青, 姚静, 苏齐鉴. 虫草素抑制TNF-α诱导的人角质形成细胞系HaCaT增殖[J]. 基础医学与临床, 2023, 43(9): 1390-1393.
[2]	陈新军, 王卿语, 陈乐, 古春昱, 武卓. 紫檀茋减轻百草枯诱导的模型大鼠肺纤维化[J]. 基础医学与临床, 2023, 43(9): 1383-1389.
[3]	江罗佳, 许海波. 短链脂肪酸乙酸钠减轻低氧/复氧诱导人肾小管上皮细胞系HK2损伤[J]. 基础医学与临床, 2023, 43(8): 1208-1214.
[4]	李想, 李晔. 非酒精性脂肪性肝病中自噬与铁死亡相互作用的研究进展[J]. 基础医学与临床, 2023, 43(8): 1294-1298.
[5]	高源, 郑刚, 齐靖, 张凤. NLRP3炎性小体在心脏病发病中的作用研究进展[J]. 基础医学与临床, 2023, 43(7): 1162-1166.
[6]	任鹏, 陈雅丽, 张娴文. 帕金森病嗅觉障碍的研究进展[J]. 基础医学与临床, 2023, 43(6): 994-997.
[7]	王星, 郭楠. 奥贝胆酸对高脂喂养的C57BL/6J小鼠糖脂稳态的影响[J]. 基础医学与临床, 2023, 43(5): 755-761.
[8]	季玮, 朱玥, 尧惠慈, 卢红艳. 白三烯C4及2型固有淋巴细胞在支气管肺发育不良中的变化及意义[J]. 基础医学与临床, 2023, 43(5): 711-716.
[9]	雷星煜, 冯雪松, 晁旭. 11β-HSD1在炎性反应、肝癌的发生发展与免疫中作用的研究进展[J]. 基础医学与临床, 2023, 43(5): 837-841.
[10]	孙莹, 杨治安, 何瑶, 余勤. HMGB1信号通路在支气管哮喘中作用的研究进展[J]. 基础医学与临床, 2023, 43(4): 690-694.
[11]	李立亚, 秦霈. 星形胶质细胞在中枢神经系统炎性疾病中作用的研究进展[J]. 基础医学与临床, 2023, 43(4): 665-668.
[12]	蒋烨, 余卓颖, 李民. 炎性反应在糖尿病神经病变发生中作用的研究进展[J]. 基础医学与临床, 2023, 43(4): 669-673.
[13]	杜丰禾, 刘暴. 血管周围脂肪组织炎性反应促进动脉粥样硬化作用机制的研究进展[J]. 基础医学与临床, 2023, 43(4): 685-689.
[14]	章远谋, 韩康, 夏瑞, 孙文健, 任晓莹, 王砚. 亚临床甲状腺功能减退症对多囊卵巢综合征患者内分泌代谢特征的影响[J]. 基础医学与临床, 2023, 43(4): 641-646.
[15]	刘芬, 胡润芳, 茅松, 徐敏, 石文静, 陈凌. 地塞米松减轻过敏性哮喘模型小鼠气道炎性反应[J]. 基础医学与临床, 2023, 43(3): 402-407.