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|本期目录/Table of Contents|

LOX-1在动脉粥样硬化中的细胞生物学效应及药物治疗新进展

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2018年第3期
页码:
348-354
栏目:
综述
出版日期:
2018-03-25

文章信息/Info

Title:
Progress in cell biological effects of LOX-1 in atherosclerosis and LOX-1 targeted medication
作者:
郑 旭1; 张丽霞1; 邓 姣2; 董海龙2
（第四军医大学：1.学员旅，2.西京医院麻醉科，陕西 西安 710032）
Author(s):
ZHENG Xu1;  ZHANG Li-xia1;  DENG Jiao2;  DONG Hai-long2
(1.Cadet Brigade, 2.Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
氧化型低密度脂蛋白; 动脉粥样硬化; 凝集素样氧化型低密度脂蛋白受体-1; 配体; 治疗药物
Keywords:
oxidative low density lipoprotein;  atherosclerosis;  Lectin-like oxidized low-density lipoprotein receptor 1;  ligands;  medication
分类号:
R543.5
DOI:
-
文献标识码:
A
摘要:
动脉粥样硬化（AS）是一种血管慢性炎症性病变，低密度脂蛋白、氧化型低密度脂蛋白和其他修饰型的脂蛋白在血管内膜下的滞留和聚积被认为是AS的起始因素。凝集素样氧化型低密度脂蛋白受体（LOX）-1在AS的发生、发展中起重要作用，介导了多种信号对血管内皮细胞的刺激，是AS斑块形成的起始因素之一。近年来，不断有新的证据发现LOX-1与细胞外不同配体的相互作用及细胞内效应，并发现多种药物通过抑制LOX-1产生抗AS的作用。本文将着重阐述近年来LOX-1在AS发生、发展中的细胞生物学效应与相关药物治疗新进展。
Abstract:
Atherosclerosis is a chronic inflammatory pathologic change of blood vessels. The retention and accumulation of low density lipoprotein, oxidized low-density lipoprotein, and other modified forms of modified lipoproteins in the intima of the vessels is considered to be one of the initiating steps for atherosclerosis. Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) has been proven to be significantly important in the development and progression of atherosclerosis. Accumulating evidence has emerged to support the diversity of extracellular legends for LOX-1 to induce intracellular effects. Current literature has revealed several drugs that could inhibit the progression of atherosclerosis through blocking or reducing LOX-1. The current review focuses on recent progress into the cell biological effects of LOX-1 in atherosclerosis and LOX-1 targeted medication.

参考文献/References

[1]Ross R,Faggiotto A,Bowen-Pope D,et al.The role of endothelial injury and platelet and macrophage interactions in atherosclerosis[J].Circulation,1984,70(5 Pt 2):III77-III82.

[2]Ross R.Atherosclerosis--an inflammatory disease[J].N Engl J Med,1999,340(2):115-126.

[3]Ross R.Mechanisms of atherosclerosis--a review[J].Adv Nephrol Necker Hosp,1990,19:79-86.

[4]Williams KJ,Tabas I.The response-to-retention hypothesis of atherogenesis reinforced[J].Curr Opin Lipidol,1998,9(5):471-474.

[5]Williams KJ,Tabas I.The response-to-retention hypothesis of early atherogenesis[J].Arterioscler Thromb Vasc Biol,1995,15(5):551-561.

[6]Maiolino G,Rossitto G,Caielli P,et al.The role of oxidized low-density lipoproteins in atherosclerosis:the myths and the facts[J].Mediators Inflamm,2013,2013:714653.

[7]Chisolm GM,Steinberg D.The oxidative modification hypothesis of atherogenesis:an overview[J].Free Radic Biol Med,2000,28(12):1815-1826.

[8]Hessler JR,Morel DW,Lewis LJ,et al.Lipoprotein oxidation and lipoprotein-induced cytotoxicity[J].Arteriosclerosis,1983,3(3):215-222.

[9]Ohki I,Ishigaki T,Oyama T,et al.Crystal structure of human lectin-like,oxidized low-density lipoprotein receptor 1 ligand binding domain and its ligand recognition mode to OxLDL[J].Structure,2005,13(6): 905-917.

[10]Nickel T,Schmauss D,Hanssen H,et al.oxLDL uptake by dendritic cells induces upregulation of scavenger-receptors, maturation and differentiation[J].Atherosclerosis,2009,205(2):442-450.

[11]Fujita Y,Kakino A,Harada-Shiba M,et al.C-reactive protein uptake by macrophage cell line via class-A scavenger receptor[J].Clin Chem,2010,56(3):478-481.

[12]Zhang D,Sun L,Zhu H,et al.Microglial LOX-1 reacts with extracellular HSP60 to bridge neuroinflammation and neurotoxicity[J].Neurochem Int,2012,61(7):1021-1035.

[13]Chen X,Zhang T,Du G.Advanced glycation end products serve as ligands for lectin-like oxidized low-density lipoprotein receptor-1(LOX-1):biochemical and binding characterizations assay[J].Cell Biochem Funct,2008,26(7):760-770.

[14]Sawamura T,Kakino A,Fujita Y.LOX-1:a multiligand receptor at the crossroads of response to danger signals[J].Curr Opin Lipidol,2012,23(5):439-445.

[15]Murphy JE,Tedbury PR,Homer-Vanniasinkam S,et al.Biochemistry and cell biology of mammalian scavenger receptors[J].Atherosclerosis,2005,182(1):1-15.

[16]Yoshimoto R,Fujita Y,Kakino A,et al.The discovery of LOX-1,its ligands and clinical significance[J].Cardiovasc Drugs Ther,2011,25(5):379-391.

[17]Xu S,Ogura S,Chen J,et al.LOX-1 in atherosclerosis:biological functions and pharmacological modifiers[J].Cell Mol Life Sci,2013,70(16):2859-2872.

[18]Akhmedov A,Rozenberg I,Paneni F,et al.Endothelial overexpression of LOX-1 increases plaque formation and promotes atherosclerosis in vivo[J].Eur Heart J,2014,35(40):2839-2848.

[19]Pirillo A,Norata GD,Catapano AL.LOX-1,OxLDL,and atherosclerosis[J].Mediators Inflamm,2013,2013:152786.

[20]Yan M,Mehta JL,Hu C.LOX-1 and obesity[J].Cardiovasc Drugs Ther,2011,25(5):469-476.

[21]Rudijanto A.The expression and down stream effect of lectin like-oxidized low density lipoprotein 1(LOX-1)in hyperglycemic state[J].Acta Med Indones,2007,39(1):36-43.

[22]Renie G,Maingrette F,Li L.Diabetic vasculopathy and the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)[J].Curr Diabetes Rev,2007,3(2):103-110.

[23]Luo P,Yan M,Frohlich ED,et al.Novel concepts in the genesis of hypertension: role of LOX-1[J].Cardiovasc Drugs Ther,2011,25(5):441-449.

[24]Kita T.LOX-1,a possible clue to the missing link between hypertension and atherogenesis[J].Circ Res,1999,84(9):1113-1115.

[25]Takanabe-Mori R,Ono K,Sowa N,et al.Lectin-like oxidized low-density lipoprotein receptor-1 is required for the adipose tissue expression of proinflammatory cytokines in high-fat diet-induced obese mice[J].Biochem Biophys Res Commun,2010,398(3):576-580.

[26]Fantuzzi G,Mazzone T.Adipose tissue and atherosclerosis: exploring the connection[J].Arterioscler Thromb Vasc Biol,2007,27(5):996-1003.

[27]Mehta JL,Li DY.Identification and autoregulation of receptor for OX-LDL in cultured human coronary artery endothelial cells[J].Biochem Biophys Res Commun,1998,248(3):511-514.

[28]Sawamura T.Molecular identification of LOX-1 and analysis of its pathophysiological role[J].Nihon Yakurigaku Zasshi,2002,119(3):145-154.

[29]Lai YS,Yang TC,Chang PY,et al.Electronegative LDL is linked to high-fat,high-cholesterol diet-induced nonalcoholic steatohepatitis in hamsters[J].J Nutr Biochem,2016,30:44-52.

[30]Apostolov EO,Shah SV,Ray D,et al.Scavenger receptors of endothelial cells mediate the uptake and cellular proatherogenic effects of carbamylated LDL[J].Arterioscler Thromb Vasc Biol,2009,29(10):1622-1630.

[31]Speer T,Owala FO,Holy EW,et al.Carbamylated low-density lipoprotein induces endothelial dysfunction[J].Eur Heart J,2014,35(43): 3021-3032.

[32]Holy EW,Akhmedov A,Speer T,et al.Carbamylated Low-Density Lipoproteins Induce a Prothrombotic State Via LOX-1:Impact on Arterial Thrombus Formation In Vivo[J].J Am Coll Cardiol,2016,68(15):1664-1676.

[33]Chen H,Li D,Sawamura T,et al.Upregulation of LOX-1 expression in aorta of hypercholesterolemic rabbits: modulation by losartan[J].Biochem Biophys Res Commun,2000,276(3):1100-1104.

[34]Gioia M,Vindigni G,Testa B,et al.Membrane Cholesterol Modulates LOX-1 Shedding in Endothelial Cells[J].PLoS One,2015,10(10):e0141270.

[35]Hong D,Li LF,Gao HC,et al.High-Density Lipoprotein Prevents Endoplasmic Reticulum Stress-Induced Downregulation of Liver LOX-1 Expression[J].PLoS One,2015,10(4):e0124285.

[36]Yang SH,Li YT,Du DY.Oxidized low-density lipoprotein-induced CD147 expression and its inhibition by high-density lipoprotein on platelets in vitro[J].Thromb Res,2013,132(6):702-711.

[37]Cominacini L,Fratta Pasini A,Garbin U,et al.The platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1 reduces the intracellular concentration of nitric oxide in endothelial cells[J].J Am Coll Cardiol,2003,41(3):499-507.

[38]Sakurai K,Cominacini L,Garbin U,et al.Induction of endothelin-1 production in endothelial cells via co-operative action between CD40 and lectin-like oxidized LDL receptor(LOX-1)[J].J Cardiovasc Pharmacol,2004,44(Suppl 1):S173-S180.

[39]Morawietz H,Rueckschloss U,Niemann B,et al.Angiotensin II induces LOX-1, the human endothelial receptor for oxidized low-density lipoprotein[J].Circulation,1999,100(9):899-902.

[40]Limor R,Kaplan M,Sawamura T,et al.Angiotensin II increases the expression of lectin-like oxidized low-density lipoprotein receptor-1 in human vascular smooth muscle cells via a lipoxygenase-dependent pathway[J].Am J Hypertens,2005,18(3):299-307.

[41]Black S,Kushner I,Samols D.C-reactive Protein[J].J Biol Chem,2004,279(47):48487-48490.

[42]Gabay C,Kushner I.Acute-phase proteins and other systemic responses to inflammation[J].N Engl J Med,1999,340(6):448-454.

[43]Shih HH,Zhang S,Cao W,et al.CRP is a novel ligand for the oxidized LDL receptor LOX-1[J].Am J Physiol Heart Circ Physiol,2009,296(5):H1643- H1650.

[44]Fujita Y,Kakino A,Nishimichi N,et al.Oxidized LDL receptor LOX-1 binds to C-reactive protein and mediates its vascular effects[J].Clin Chem,2009,55(2):285-294.

[45]Inoue N,Sawamura T.Lectin-like oxidized LDL receptor-1 as extracellular chaperone receptor: its versatile functions and human diseases[J].Methods,2007,43(3):218-222.

[46]Singh R,Barden A,Mori T,et al.Advanced glycation end-products:a review[J].Diabetologia,2001,44(2):129-146.

[47]Tan KC,Shiu SW,Wong Y,et al.Soluble lectin-like oxidized low density lipoprotein receptor-1 in type 2 diabetes mellitus[J].J Lipid Res,2008,49(7):1438-1444.

[48]Shiu SW,Wong Y,Tan KC.Effect of advanced glycation end products on lectin-like oxidized low density lipoprotein receptor-1 expression in endothelial cells[J].J Atheroscler Thromb,2012,19(12):1083-1092.

[49]Xie J,Zhu H,Guo L,et al.Lectin-like oxidized low-density lipoprotein receptor-1 delivers heat shock protein 60-fused antigen into the MHC class I presentation pathway[J].J Immunol,2010,185(4):2306-2313.

[50]Nagase M,Ando K,Nagase T,et al.Redox-sensitive regulation of lox-1 gene expression in vascular endothelium[J].Biochem Biophys Res Commun,2001,281(3):720-725.

[51]Lubrano V,Balzan S.LOX-1 and ROS,inseparable factors in the process of endothelial damage[J].Free Radic Res,2014,48(8):841-848.

[52]Murase T,Kume N,Korenaga R,et al.Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells[J].Circ Res,1998,83(3):328-333.

[53]Ding Z,Liu S,Deng X,et al.Hemodynamic shear stress modulates endothelial cell autophagy: Role of LOX-1[J].Int J Cardiol,2015,184:86-95.

[54]Pirillo A,Uboldi P,Ferri N,et al.Upregulation of lectin-like oxidized low density lipoprotein receptor 1(LOX-1)expression in human endothelial cells by modified high density lipoproteins[J].Biochem Biophys Res Commun,2012,428(2):230-233.

[55]Hashizume M,Mihara M.Blockade of IL-6 and TNF-alpha inhibited oxLDL-induced production of MCP-1 via scavenger receptor induction[J].Eur J Pharmacol,2012,689(1-3):249-254.

[56]Arjuman A,Chandra NC.Differential pro-inflammatory responses of TNF-alpha receptors(TNFR1 and TNFR2)on LOX-1 signalling[J].Mol Biol Rep,2015,42(6):1039-1047.

[57]Yamagata K,Tusruta C,Ohtuski A,et al.Docosahexaenoic acid decreases TNF-alpha-induced lectin-like oxidized low-density lipoprotein receptor-1 expression in THP-1 cells[J].Prostaglandins Leukot Essent Fatty Acids,2014,90(4):125-132.

[58]Wang TM,Chen CJ,Lee TS,et al.Docosahexaenoic acid attenuates VCAM-1 expression and NF-kappaB activation in TNF-alpha-treated human aortic endothelial cells[J].J Nutr Biochem,2011,22(2):187-194.

[59]Satoh M,Minami Y,Takahashi Y,et al.A cellular microRNA,let-7i, is a novel biomarker for clinical outcome in patients with dilated cardiomyopathy[J].J Card Fail,2011,17(11):923-929.

[60]Ding Z,Wang X,Schnackenberg L,et al.Regulation of autophagy and apoptosis in response to ox-LDL in vascular smooth muscle cells, and the modulatory effects of the microRNA hsa-let-7 g[J].Int J Cardiol,2013, 168(2):1378-1385.

[61]Bao MH, Feng X, Zhang YW, et al. Let-7 in cardiovascular diseases,heart development and cardiovascular differentiation from stem cells[J].Int J Mol Sci,2013,14(11):23086-23102.

[62]Bao MH,Zhang YW,Lou XY,et al.Protective effects of let-7a and let-7b on oxidized low-density lipoprotein induced endothelial cell injuries[J].PLoS One,2014,9(9):e106540.

[63]Chen KC,Hsieh IC,Hsi E,et al.Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX-1[J].Journal of Cell Science,2011,124(23):4115-4124.

[64]Chui PC,Guan HP,Lehrke M,et al.PPARgamma regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1[J].J Clin Invest,2005,115(8):2244-2256.

[65]Xu L,Wang S,Li B,et al.A protective role of ciglitazone in ox-LDL-induced rat microvascular endothelial cells via modulating PPARgamma-dependent AMPK/eNOS pathway[J].J Cell Mol Med,2015,19(1):92-102.

[66]Li L,Renier G.The oral anti-diabetic agent,gliclazide,inhibits oxidized LDL-mediated LOX-1 expression,metalloproteinase-9 secretion and apoptosis in human aortic endothelial cells[J].Atherosclerosis,2009,204(1):40-46.

[67]Rasouli N,Yao-Borengasser A,Varma V,et al.Association of scavenger receptors in adipose tissue with insulin resistance in nondiabetic humans[J].Arterioscler Thromb Vasc Biol,2009,29(9):1328-1335.

[68]Chen JW,Zhou SB,Tan ZM.Aspirin and pravastatin reduce lectin-like oxidized low density lipoprotein receptor-1 expression,adhesion molecules and oxidative stress in human coronary artery endothelial cells[J].Chin Med J(Engl),2010,123(12):1553-1556.

[69]Zhi Z,Pengfei Z,Xiaoyi T,et al.Adiponectin ameliorates angiotensin II-induced vascular endothelial damage[J].Cell Stress Chaperones,2014,19(5):705-713.

[70]Bao MH,Zhang YW,Zhou HH.Paeonol suppresses oxidized low-density lipoprotein induced endothelial cell apoptosis via activation of LOX-1/p38MAPK/NF-kappaB pathway[J].J Ethnopharmacol,2013,146(2):543-551.

[71]Qin M,Luo Y,Meng XB,et al.Myricitrin attenuates endothelial cell apoptosis to prevent atherosclerosis: An insight into PI3K/Akt activation and STAT3 signaling pathways[J].Vascul Pharmacol,2015,70:23-34.

[72]Lin J,Xu Y,Zhao T,et al.Genistein suppresses smooth muscle cell-derived foam cell formation through tyrosine kinase pathway[J].Biochem Biophys Res Commun,2015,463(4):1297-1304.

[73]Cai Y,Li JD,Yan C.Vinpocetine attenuates lipid accumulation and atherosclerosis formation[J].Biochem Biophys Res Commun,2013,434(3):439-443.

[74]Hofnagel O,Luechtenborg B,Eschert H,et al.Pravastatin inhibits expression of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)in Watanabe heritable hyperlipidemic rabbits:a new pleiotropic effect of statins[J].Arterioscler Thromb Vasc Biol,2006,26(3):604-610.

[75]Li D,Chen H,Romeo F,et al.Statins modulate oxidized low-density lipoprotein-mediated adhesion molecule expression in human coronary artery endothelial cells:role of LOX-1[J].J Pharmacol Exp Ther,2002,302(2):601-605.

[76]Liu L,Hu Q,Wu H,et al.Protective role of n6/n3 PUFA supplementation with varying DHA/EPA ratios against atherosclerosis in mice[J].J Nutr Biochem,2016,32:171-180.

[77]Toba H,Shimizu T,Miki S,et al.Calcium[corrected]channel blockers reduce angiotensin II-induced superoxide generation and inhibit lectin-like oxidized low-density lipoprotein receptor-1 expression in endothelial cells[J].Hypertens Res,2006,29(2):105-116.

备注/Memo

备注/Memo:
收稿日期：2017-03-06.通讯作者：邓姣，主治医师，博士，主要从事神经损伤及防护研究 Email:dengjiao1984@gmail.com 作者简介：郑旭，本科生 Email:3052012043@student.fmmu.edu.cn. 共同第一作者：张丽霞，本科生 Email:3032013344@student.fmmu.edu.cn
更新日期/Last Update: 1900-01-01