脂蛋白相关磷脂酶A2及其与糖尿病视网膜病变相关性的进展
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摘要
糖尿病视网膜病变(diabetic retinopathy,DR)是导致不可逆性眼盲的重要原因之一,DR发病与动脉粥样硬化密切相关,其治疗干预靶点成为当今研究的热点。脂蛋白相关磷脂酶A2(lipoproteinassociated phospholipase A2,Lp-PLA2)是一种新型炎症因子,与动脉粥样硬化及炎症反应等相关。了解Lp-PLA2与DR相关性研究现状可能为进一步研究DR治疗提供新的思路。
Diabetic retinopathy(DR) is one of the important causes of irreversible blindness. DR is closely related to atherosclerosis, and its therapeutic intervention target has become a hot topic in current research. Lipoproteinassociated phospholipase A2(Lp-PLA2), as a new inflammation factor, is related to atherosclerosis and inflammatory response. Understanding the current correlation of Lp-PLA2 and DR may provide a novel option in future treatment of DR.
Diabetic retinopathy(DR) is one of the important causes of irreversible blindness. DR is closely related to atherosclerosis, and its therapeutic intervention target has become a hot topic in current research. Lipoproteinassociated phospholipase A2(Lp-PLA2), as a new inflammation factor, is related to atherosclerosis and inflammatory response. Understanding the current correlation of Lp-PLA2 and DR may provide a novel option in future treatment of DR.
引文
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2.中华医学会眼科学会眼底病学组.我国糖尿病视网膜病变临床诊疗指南(2014年)[J].中华眼科杂志,2014,50(11):851-865.Department of Ophthalmology Chinese Medical Association.Guidelines for clinical diagnosis and treatment of diabetic retinopathy in China(2014)[J].Chinese Journal of Ophthalmology,2014,50(11):851-865.
3.Lim LS,Ling LH,Cheung CM,et al.Relationship of systemic endothelial function and peripheral arterial stiffness with diabetic retinopathy[J].Br J Ophthalmol,2015,99(6):837-841.
4.丁秋爱,游志鹏.糖尿病视网膜病变与免疫炎症关系的研究进展[J].南昌大学学报(医学版),2017,57(6):97-100.DING Qiu’ai,YOU Zhipeng.Research progress on the relationship between diabetic retinopathy and immune inflammation[J].Acta Academiae Medicinae Jiangxi,2017,57(6):97-100.
5.肖玥言,袁梦克,郗平,等.颈动脉斑块与糖尿病视网膜病变的相关性[J].中华医学杂志,2017,97(24):1871-1874.XIAO Yueyan,YUAN Mengke,XI Ping,et al.Relationship between carotid plaque and diabetic retinopathy in type 2 diabetes mellitus patients[J].National Medical Journal of China,2017,97(24):1871-1874.
6.Ait-Oufella H,Mallat Z,Tedgui A.Lp-PLA2 and sPLA2:cardiovascular biomarkers[J].Med Sci(Paris),2014,30(5):526-531.
7.Fitzpatrick AL,Irizarry MC,Cushman M,et al.Lipoprotein-associated phospholipase A2 and risk of dementia in the Cardiovascular Health Study[J].Atherosclerosis,2014,235(2):384-391.
8.Hou L,Chen S,Yu H,et al.A ssociations of PL A2G7 gene polymorphisms with plasma lipoprotein-associated phospholipase A2activity and coronary heart disease in a Chinese Han population:the Beijing atherosclerosis study[J].Hum Genet,2009,125(1):11-20.
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10.Tellis CC,Tselepis AD.Pathophysiological role and clinical significance of lipoprotein-associated phospholipase A?(Lp-PLA?)bound to LDLand HDL[J].Curr Pharm Des,2014,20(40):6256-6269.
11.Donato LJ,Meeusen JW,Callanan H,et al.Advantages of the lipoprotein-associated phospholipase A2 activity assay[J].Clin Biochem,2016,49(1/2):172-5.
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16.Maiolino G,Bisogni V,Rossitto G,et al.Lipoprotein-associated phospholipase A2 prognostic role in atherosclerotic complications[J].World J Cardiol,2015,7(10):609-20.
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18.Garg S,Madhu SV,Suneja S.Lipoprotein associated phospholipase A2activity&its correlation with oxidized LDL&glycaemic status in early stages of type-2 diabetes mellitus[J].Indian J Med Res,2015,141(1):107-114.
19.Sánchez-Quesada JL,Vinagre I,de Juan-Franco E,et al.Effect of improving glycemic control in patients with type 2 diabetes mellitus on low-density lipoprotein size,electronegative low-density lipoprotein and lipoprotein-associated phospholipase A2 distribution[J].Am JCardiol,2012,110(1):67-71.
20.Mayer O,SeidlerováJ,FilipovskyJ,et al.Unexpected inverse relationship between impaired glucose metabolism and lipoproteinassociated phospholipase A2 activity in patients with stable vascular disease[J].Eur J Intern Med,2014,25(6):556-560.
21.Onat A,Hergen?G,Can G,et al.Dual activity of serum lipoproteinassociated phospholipase A(2)y ielding positive and inverse associations with cardiometabolic risk[J].Clin Chem Lab Med,2011,49(8):1349-1357.
22.Alkuraishy HM,Al-Gareeb AI,Waheed HJ.Lipoprotein-associated phospholipase A2 is linked with poor cardio-metabolic profile in patients with ischemic stroke:a study of effects of statins[J].J Neurosci Rural Pract,2018,9(4):496-503.
23.Zheng D,Cai A,Xu R,et al.Effects and potential mechanism of atorvastatin treatment on Lp-PLA2 in rats with dyslipidemia[J].Arch Med Sci,2018,14(3):629-634.
24.Asciutto G,Edsfeldt A,Dias NV,et al.Treatment with beta-blockers is associated with lower levels of Lp-PLA2 and suPAR in carotid plaques[J].Cardiovasc Pathol,2013,22(6):438-443.
25.Winkler K,Winkelmann BR,Scharnagl H,et al.Platelet-activating factor acetylhydrolase activity indicates angiographic coronary artery disease independently of systemic inflammation and other risk factors:the Ludwigshafen Risk and Cardiovascular Health Study[J].Circulation,2005,111(8):980-987.
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27.Serruys PW,García-García HM,Buszman P,et al.Effects of the direct lipoprotein-associated phospholipase A(2)inhibitor darapladib on human coronary atherosclerotic plaque[J].Circulation,2008,118(11):1172-1182.
28.Mannheim D,Herrmann J,Versari D,et al.Enhanced expression of Lp-PLA2 and lysophosphatidylcholine in symptomatic carotid atherosclerotic plaques[J].Stroke,2008,39(5):1448-1455.
29.Singh U,Zhong S,Xiong M,et al.Increased plasma non-esterified fatty acids and platelet-activating factor acetylhydrolase are associated with susceptibility to atherosclerosis in mice[J].Clin Sci(Lond),2004,106(4):421-432.
30.Ikonomidis I,Kadoglou NN,Tritakis V,et al.Association of LpPLA2 with digital reactive hyperemia,coronary flow reserve,carotid atherosclerosis and arterial stiffness in coronary artery disease[J].Atherosclerosis,2014,234(1):34-41.
31.Di Pietro N,Formoso G,Pandolfi A.Physiology and pathophysiology of oxLDL uptake by vascular wall cells in atherosclerosis[J].Vascul Pharmacol,2016,84:1-7.
32.汪晶,潘永明,徐孝平,等.高脂诱导五指山小型猪动脉粥样硬化模型的建立及Lp-PLA2的表达调控[J].中国实验动物学报,2017,25(2):194-200.WANG Jing,PAN Yongming,XU Xiaoping,et al.Establishment of a Wuzhishan minipig model of atherosclerosis induced by high fat/cholesterol diet and regulation of Lp-PLA2 expression[J].Acta Laboratorium Animalis Scientia Sinica,2017,25(2):194-200.
33.Mattina A,Rosenbaum D,Bittar R,et al.Lipoprotein-associated phospholipase A?activity is increased in patients with definite familial hy percholesterolemia compared w ith other forms of hypercholesterolemia[J].Nutr Metab Cardiovasc Dis,2018,28(5):517-523.
34.Krebs A,Doerfer J,Krause A,et al.Lipoprotein-associated phospholipase A2 activity and low-density lipoprotein subfractions after a 2-year treatment with atorvastatin in adolescents with type 1diabetes[J].J Pediatr Endocrinol Metab,2016,29(10):1181-1186.
35.Kumar B,Kowluru A,Kowluru RA.Lipotoxicity augments glucotoxicityinduced mitochondrial damage in the development of diabetic retinopathy[J].Invest Ophthalmol Vis Sci,2015,56(5):2985-2992.
36.Chew EY,Davis MD,Danis RP,et al.The effects of medical management on the progression of diabetic retinopathy in persons with type 2diabetes:the Action to Control Cardiovascular Risk in Diabetes(ACCORD)Eye Study[J].Ophthalmology,2014,121(12):2443-2451.
37.Ibrahim AS,Elshafey S,Sellak H,et al.A lipidomic screen of hy perglycemia-treated HRECs link s 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPHoxidase[J].J Lipid Res,2015,56(3):599-611.
38.Tremblay J,Hamet P.Biomarkers of vascular complications in type 2diabetes[J].Metabolism,2015,64(3 Suppl 1):S28-S32.
39.Toth PP,Simko RJ,Palli SR,et al.The impact of serum lipids on risk for microangiopathy in patients with type 2 diabetes mellitus[J].Cardiovasc Diabetol,2012,11:109.
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41.Papavasileiou E,Davoudi S,Roohipoor R,et al.Association of serum lipid levels with retinal hard exudate area in African Americans with type 2 diabetes[J].Graefes Arch Clin Exp Ophthalmol,2017,255(3):509-517.
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2.中华医学会眼科学会眼底病学组.我国糖尿病视网膜病变临床诊疗指南(2014年)[J].中华眼科杂志,2014,50(11):851-865.Department of Ophthalmology Chinese Medical Association.Guidelines for clinical diagnosis and treatment of diabetic retinopathy in China(2014)[J].Chinese Journal of Ophthalmology,2014,50(11):851-865.
3.Lim LS,Ling LH,Cheung CM,et al.Relationship of systemic endothelial function and peripheral arterial stiffness with diabetic retinopathy[J].Br J Ophthalmol,2015,99(6):837-841.
4.丁秋爱,游志鹏.糖尿病视网膜病变与免疫炎症关系的研究进展[J].南昌大学学报(医学版),2017,57(6):97-100.DING Qiu’ai,YOU Zhipeng.Research progress on the relationship between diabetic retinopathy and immune inflammation[J].Acta Academiae Medicinae Jiangxi,2017,57(6):97-100.
5.肖玥言,袁梦克,郗平,等.颈动脉斑块与糖尿病视网膜病变的相关性[J].中华医学杂志,2017,97(24):1871-1874.XIAO Yueyan,YUAN Mengke,XI Ping,et al.Relationship between carotid plaque and diabetic retinopathy in type 2 diabetes mellitus patients[J].National Medical Journal of China,2017,97(24):1871-1874.
6.Ait-Oufella H,Mallat Z,Tedgui A.Lp-PLA2 and sPLA2:cardiovascular biomarkers[J].Med Sci(Paris),2014,30(5):526-531.
7.Fitzpatrick AL,Irizarry MC,Cushman M,et al.Lipoprotein-associated phospholipase A2 and risk of dementia in the Cardiovascular Health Study[J].Atherosclerosis,2014,235(2):384-391.
8.Hou L,Chen S,Yu H,et al.A ssociations of PL A2G7 gene polymorphisms with plasma lipoprotein-associated phospholipase A2activity and coronary heart disease in a Chinese Han population:the Beijing atherosclerosis study[J].Hum Genet,2009,125(1):11-20.
9.Canning P,Kenny BA,Prise V,et al.Lipoprotein-associated phospholipase A2(Lp-PLA2)as a therapeutic target to prevent retinal vasopermeability during diabetes[J].Proc Natl Acad Sci USA,2016,113(26):7213-7218.
10.Tellis CC,Tselepis AD.Pathophysiological role and clinical significance of lipoprotein-associated phospholipase A?(Lp-PLA?)bound to LDLand HDL[J].Curr Pharm Des,2014,20(40):6256-6269.
11.Donato LJ,Meeusen JW,Callanan H,et al.Advantages of the lipoprotein-associated phospholipase A2 activity assay[J].Clin Biochem,2016,49(1/2):172-5.
12.Gazi I,Lourida ES,Filippatos T,et al.Lipoprotein-associated phospholipase A2 activity is a marker of small,dense LDL particles in human plasma[J].Clin Chem,2005,51(12):2264-2273.
13.Cao J,Hsu YH,Li S,et al.Structural basis of specific interactions of Lp-PLA2 with HDL revealed by hydrogen deuterium exchange mass spectrometry[J].J Lipid Res,2013,54(1):127-133.
14.Xu RX,Zhang Y,Li XL,et al.Relationship between plasma phospholipase A2 concentrations and lipoprotein subfractions in patients with stable coronary artery disease[J].Clin Chim Acta,2015,446:195-200.
15.Grallert H,Dupuis J,Bis JC,et al.Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease:Meta-analysis of genome-wide association studies from five community-based studies[J].Eur Heart J,2012,33(2):238-251.
16.Maiolino G,Bisogni V,Rossitto G,et al.Lipoprotein-associated phospholipase A2 prognostic role in atherosclerotic complications[J].World J Cardiol,2015,7(10):609-20.
17.Qi Y,Zhao D,Jia Z,et al.A previously unreported impact of a PLA2G7gene polymorphism on the plasma levels of lipoprotein-associated phospholipase A2 activity and mass[J].Sci Rep,2016,6:37465.
18.Garg S,Madhu SV,Suneja S.Lipoprotein associated phospholipase A2activity&its correlation with oxidized LDL&glycaemic status in early stages of type-2 diabetes mellitus[J].Indian J Med Res,2015,141(1):107-114.
19.Sánchez-Quesada JL,Vinagre I,de Juan-Franco E,et al.Effect of improving glycemic control in patients with type 2 diabetes mellitus on low-density lipoprotein size,electronegative low-density lipoprotein and lipoprotein-associated phospholipase A2 distribution[J].Am JCardiol,2012,110(1):67-71.
20.Mayer O,SeidlerováJ,FilipovskyJ,et al.Unexpected inverse relationship between impaired glucose metabolism and lipoproteinassociated phospholipase A2 activity in patients with stable vascular disease[J].Eur J Intern Med,2014,25(6):556-560.
21.Onat A,Hergen?G,Can G,et al.Dual activity of serum lipoproteinassociated phospholipase A(2)y ielding positive and inverse associations with cardiometabolic risk[J].Clin Chem Lab Med,2011,49(8):1349-1357.
22.Alkuraishy HM,Al-Gareeb AI,Waheed HJ.Lipoprotein-associated phospholipase A2 is linked with poor cardio-metabolic profile in patients with ischemic stroke:a study of effects of statins[J].J Neurosci Rural Pract,2018,9(4):496-503.
23.Zheng D,Cai A,Xu R,et al.Effects and potential mechanism of atorvastatin treatment on Lp-PLA2 in rats with dyslipidemia[J].Arch Med Sci,2018,14(3):629-634.
24.Asciutto G,Edsfeldt A,Dias NV,et al.Treatment with beta-blockers is associated with lower levels of Lp-PLA2 and suPAR in carotid plaques[J].Cardiovasc Pathol,2013,22(6):438-443.
25.Winkler K,Winkelmann BR,Scharnagl H,et al.Platelet-activating factor acetylhydrolase activity indicates angiographic coronary artery disease independently of systemic inflammation and other risk factors:the Ludwigshafen Risk and Cardiovascular Health Study[J].Circulation,2005,111(8):980-987.
26.毛洋,刘小琼,王洪梅,等.细胞间黏附分子1、血管细胞黏附分子1促进兔动脉粥样硬化斑块内血管新生[J].中国动脉硬化杂志,2014,22(3):217-222.MAO Yang,LIU Xiaoqiong,WANG Hongmei,et al.Regulation of plaque neovascularization by intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 at the advanced stages of atherosclerosis[J].Chinese Journal of Arteriosclerosis,2014,22(3):217-222.
27.Serruys PW,García-García HM,Buszman P,et al.Effects of the direct lipoprotein-associated phospholipase A(2)inhibitor darapladib on human coronary atherosclerotic plaque[J].Circulation,2008,118(11):1172-1182.
28.Mannheim D,Herrmann J,Versari D,et al.Enhanced expression of Lp-PLA2 and lysophosphatidylcholine in symptomatic carotid atherosclerotic plaques[J].Stroke,2008,39(5):1448-1455.
29.Singh U,Zhong S,Xiong M,et al.Increased plasma non-esterified fatty acids and platelet-activating factor acetylhydrolase are associated with susceptibility to atherosclerosis in mice[J].Clin Sci(Lond),2004,106(4):421-432.
30.Ikonomidis I,Kadoglou NN,Tritakis V,et al.Association of LpPLA2 with digital reactive hyperemia,coronary flow reserve,carotid atherosclerosis and arterial stiffness in coronary artery disease[J].Atherosclerosis,2014,234(1):34-41.
31.Di Pietro N,Formoso G,Pandolfi A.Physiology and pathophysiology of oxLDL uptake by vascular wall cells in atherosclerosis[J].Vascul Pharmacol,2016,84:1-7.
32.汪晶,潘永明,徐孝平,等.高脂诱导五指山小型猪动脉粥样硬化模型的建立及Lp-PLA2的表达调控[J].中国实验动物学报,2017,25(2):194-200.WANG Jing,PAN Yongming,XU Xiaoping,et al.Establishment of a Wuzhishan minipig model of atherosclerosis induced by high fat/cholesterol diet and regulation of Lp-PLA2 expression[J].Acta Laboratorium Animalis Scientia Sinica,2017,25(2):194-200.
33.Mattina A,Rosenbaum D,Bittar R,et al.Lipoprotein-associated phospholipase A?activity is increased in patients with definite familial hy percholesterolemia compared w ith other forms of hypercholesterolemia[J].Nutr Metab Cardiovasc Dis,2018,28(5):517-523.
34.Krebs A,Doerfer J,Krause A,et al.Lipoprotein-associated phospholipase A2 activity and low-density lipoprotein subfractions after a 2-year treatment with atorvastatin in adolescents with type 1diabetes[J].J Pediatr Endocrinol Metab,2016,29(10):1181-1186.
35.Kumar B,Kowluru A,Kowluru RA.Lipotoxicity augments glucotoxicityinduced mitochondrial damage in the development of diabetic retinopathy[J].Invest Ophthalmol Vis Sci,2015,56(5):2985-2992.
36.Chew EY,Davis MD,Danis RP,et al.The effects of medical management on the progression of diabetic retinopathy in persons with type 2diabetes:the Action to Control Cardiovascular Risk in Diabetes(ACCORD)Eye Study[J].Ophthalmology,2014,121(12):2443-2451.
37.Ibrahim AS,Elshafey S,Sellak H,et al.A lipidomic screen of hy perglycemia-treated HRECs link s 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPHoxidase[J].J Lipid Res,2015,56(3):599-611.
38.Tremblay J,Hamet P.Biomarkers of vascular complications in type 2diabetes[J].Metabolism,2015,64(3 Suppl 1):S28-S32.
39.Toth PP,Simko RJ,Palli SR,et al.The impact of serum lipids on risk for microangiopathy in patients with type 2 diabetes mellitus[J].Cardiovasc Diabetol,2012,11:109.
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