孤立低高密度脂蛋白胆固醇表型与血浆miR-9-3p、miR-28-5p的表达分析
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摘要
目的探讨孤立低高密度脂蛋白胆固醇(HDL-C)表型血浆miR-9-3p和miR-28-5p的变化模式及其相关性。方法选取唐山市工人医院体检中心2014年1月至2015年12月174例健康体检者资料,收集其外周血血浆样本。根据血清HDL-C水平分为血脂正常表型组(86例)和孤立低HDL-C表型组(88例)。实时荧光定量聚合酶链反应(qPCR)法测定血浆miR-9-3p和miR-28-5p的表达水平。结果脂代谢表型正常组和孤立低HDL-C表型组血浆中miR-9-3p的检出率分别为86.05%(74/86)和64.78%(57/88),差异有统计学意义(χ2=10.58,P=0.001);女性miR-9-3p水平在脂代谢正常组和孤立低HDL-C异常表型组血浆中的表达水平均高于男性[正常组:0.041(0.024,0.111)vs.0.018(0.009,0.039),Z=3.05,P=0.002;孤立低HDL-C表型组:0.029(0.024,0.059)vs.0.013(0.007,0.027),Z=3.35,P=0.001]。线性回归显示,表观健康者血浆miR-9-3p的相对表达水平与性别(β=-1.337,P<0.001)、血清HDL-C(β=1.638,P=0.041)、空腹血糖(β=0.475,P=0.044)相关。血浆miR-28-5p女性组高于男性组,差异有统计学意义[0.003(0.002,0.008)vs.0.004(0.003,0.011),P=0.028],而不同表型组中男、女比较差异无统计学意义(P>0.05)。结论血浆miR-9-3p是孤立低HDL-C表型的分子病理特征,性别、血清HDL-C、空腹血糖是其循环水平变化的主要影响因素。
Objective To investigate the change pattern and the correlationof miR-9-3 p and miR-28-5 p in plasma with isolated low(HDL-C)phenotype.Methods The data of 174 apparent health examinees from January 2014 to December 2015 in Tangshan Gongren Hospital Physical Examination Center were collected to collect peripheral blood plasma samples.According to the level of serum HDL-C,the patients were divided into normal lipid phenotype group(86 cases)and isolated low HDL-C phenotype group(88 cases).The expression levels of microRNA-9-3 p and microRNA-28-5 p in plasma were determined by fluorescence quantitative polymerase chain reaction(qPCR).Results The detection rates of microRNA-9-3 p in plasma of normal lipid metabolism phenotype group and isolated low HDL-C phenotype group were 86.05%(74/86)and 64.78%(57/88),respectively,and the difference was statistically significant(χ2=10.58,P=0.001).The expression of microRNA-9-3 p in plasma of women with normal lipid metabolism and isolated low HDL-C abnormal phenotype was higher than that of men in the normal lipid phenotype group[in the normal group:0.041(0.024,0.111)vs.0.018(0.009,0.039),Z=3.05,P=0.002;in the isolated low HDL-C phenotype group:0.029(0.024,0.059)vs.0.013(0.007,0.027),Z=3.35,P=0.001].Linear regression showed that the relative expression level of plasma microRNA-9-3 p was correlated with gender(β=-1.337,P<0.001),serum HDL-C(β=1.638,P=0.041),fasting blood glucose(β=0.475,P=0.044).The level of plasma microRNA-28-5 p in female group was higher than that in male group,and the difference was statistically significant[0.003(0.002,0.008)vs.0.004(0.003,0.011),P=0.028]while there was no significant difference among the other groups(P>0.05).Conclusion Serum microRNA-9-3 p is a molecular pathological feature of isolated low HDL-C phenotype.Gender,serum HDL-C and fasting blood-glucose are the main influencing factors of circulatory changes.
Objective To investigate the change pattern and the correlationof miR-9-3 p and miR-28-5 p in plasma with isolated low(HDL-C)phenotype.Methods The data of 174 apparent health examinees from January 2014 to December 2015 in Tangshan Gongren Hospital Physical Examination Center were collected to collect peripheral blood plasma samples.According to the level of serum HDL-C,the patients were divided into normal lipid phenotype group(86 cases)and isolated low HDL-C phenotype group(88 cases).The expression levels of microRNA-9-3 p and microRNA-28-5 p in plasma were determined by fluorescence quantitative polymerase chain reaction(qPCR).Results The detection rates of microRNA-9-3 p in plasma of normal lipid metabolism phenotype group and isolated low HDL-C phenotype group were 86.05%(74/86)and 64.78%(57/88),respectively,and the difference was statistically significant(χ2=10.58,P=0.001).The expression of microRNA-9-3 p in plasma of women with normal lipid metabolism and isolated low HDL-C abnormal phenotype was higher than that of men in the normal lipid phenotype group[in the normal group:0.041(0.024,0.111)vs.0.018(0.009,0.039),Z=3.05,P=0.002;in the isolated low HDL-C phenotype group:0.029(0.024,0.059)vs.0.013(0.007,0.027),Z=3.35,P=0.001].Linear regression showed that the relative expression level of plasma microRNA-9-3 p was correlated with gender(β=-1.337,P<0.001),serum HDL-C(β=1.638,P=0.041),fasting blood glucose(β=0.475,P=0.044).The level of plasma microRNA-28-5 p in female group was higher than that in male group,and the difference was statistically significant[0.003(0.002,0.008)vs.0.004(0.003,0.011),P=0.028]while there was no significant difference among the other groups(P>0.05).Conclusion Serum microRNA-9-3 p is a molecular pathological feature of isolated low HDL-C phenotype.Gender,serum HDL-C and fasting blood-glucose are the main influencing factors of circulatory changes.
引文
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[11]LIU J,LIU X Q,LIU Y,et al.MicroRNA 28-5p regulates ATP-binding cassette transporter A1via inhibiting extracellular signal-regulated kinase 2[J].Mol Med Rep,2016,13(1):433-440.
[12]Tq D A V,TE J,KIM T,et al.MicroRNA-144regulates hepatic ATP binding cassette transporter A1and plasma high-density lipoprotein after activation of the nuclear receptor farnesoid X receptor[J].Circ Res,2013,112(12):1602-1612
[13]YAN C,CHEN J,MIN L,et al.A decrease in hepatic microRNA-9expression impairs gluconeogenesis by targeting FOXO1in obese mice[J].Diabetologia,2016,59(7):1524-1532.
[14]ZHANG J,CHINTAL V,SHIH T,et al.MicroRNA-9is an activation-induced regulator of PDGFR-beta expression in cardiomyocytes[J].J Mol Cell Cardiol,2011,51(3):337-346.
[15]XU J,HU G,LU M,et al.MiR-9reduces human acyl-coenzyme A:cholesterol acyltransferase-1to decrease THP-1macrophage-derived foam cell formation[J].Acta Biochim Biophys Sin(Shanghai),2013,45(11):953-962..
[16]米春芳,刘庆平.血浆低密度脂蛋白和高密度脂蛋白亚组分的临床意义及检测研究进展[J].中国动脉硬化杂志,2017,25(10):1054-1060.
[2] HUXLEY R R,BARZI F,LAM T H,et al.Isolated low levels of high-density lipoprotein cholesterol are associated with an increased risk of coronary heart disease-an individual participant data meta-analysis of 23studies in the asia-pacific region[J].Circulation,2011,124(20):2056-2064.
[3]刘梦迪,李金容,吴冰,等.microRNAs:高密度脂蛋白胆固醇干预治疗心血管疾病的新靶标[J].国际检验医学杂志,2016,37,(20):2867-2870.
[4] CAO Y,JIANG X,MA H,et al.SIRT1and insulin resistance[J].J Diabetes Complicat,2016,30:178-183.
[5] LIU J,LIU Y,SUN Y,et al.miR-28-5p Involved in LXRABCA1pathway is increased in the plasma of unstable angina patients[J].Heart,Lung Circ,2015,24:724-730.
[6]吴冰,曲淑君,孟军华,等.唐山市城镇健康居民体检血清高密度脂蛋白胆固醇水平的分布[J].中华检验医学杂志,2015,38(2):120-123.
[7] YETUKURI L,SODERLUND S,KOIVUNIEMI A,et al.Composition and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol[J].J Lipid Res,2010,51:2341-2351.
[8] HOLVEN K B,RETTERSTOL K,UELAND T,et al.Subjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype[J].PLoS ONE,2013,8:e78241.
[9] VAZZANA N,GANCI A,CEFLU A B,et al.Enhanced lipid peroxidation and platelet activation as potential contributors to increased cardiovascular risk in the low-HDL phenotype[J].J Am Heart Assoc,2013,2:e000063.
[10]ROTLLAN N,RAMIREZ C M,ARYAL B,et al.Therapeutic silencing of microRNA-33inhibits the progression of atherosclerosis in Ldlr-/-mice——brief report[J].Arterioscler Thromb Vasc Biol,2013,33(8):1973-1977.
[11]LIU J,LIU X Q,LIU Y,et al.MicroRNA 28-5p regulates ATP-binding cassette transporter A1via inhibiting extracellular signal-regulated kinase 2[J].Mol Med Rep,2016,13(1):433-440.
[12]Tq D A V,TE J,KIM T,et al.MicroRNA-144regulates hepatic ATP binding cassette transporter A1and plasma high-density lipoprotein after activation of the nuclear receptor farnesoid X receptor[J].Circ Res,2013,112(12):1602-1612
[13]YAN C,CHEN J,MIN L,et al.A decrease in hepatic microRNA-9expression impairs gluconeogenesis by targeting FOXO1in obese mice[J].Diabetologia,2016,59(7):1524-1532.
[14]ZHANG J,CHINTAL V,SHIH T,et al.MicroRNA-9is an activation-induced regulator of PDGFR-beta expression in cardiomyocytes[J].J Mol Cell Cardiol,2011,51(3):337-346.
[15]XU J,HU G,LU M,et al.MiR-9reduces human acyl-coenzyme A:cholesterol acyltransferase-1to decrease THP-1macrophage-derived foam cell formation[J].Acta Biochim Biophys Sin(Shanghai),2013,45(11):953-962..
[16]米春芳,刘庆平.血浆低密度脂蛋白和高密度脂蛋白亚组分的临床意义及检测研究进展[J].中国动脉硬化杂志,2017,25(10):1054-1060.
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