动脉粥样硬化患者外周血miR-152表达变化机制及其与血脂水平的相关性
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摘要
目的探讨动脉粥样硬化(AS)患者外周血miR-152及其启动子区DNA甲基化水平改变,并分析其与血脂水平的相关性。方法选择经颈动脉多普勒超声检查确诊为AS患者40例(AS组),并选择同期健康体检者40例作为对照(对照组)。生化分析仪检测两组患者血脂水平;实时荧光定量PCR(RT-qPCR)检测两组患者外周血miR-152的表达水平;巢式降落式甲基化特异性PCR(nt-MSP)检测两组患者外周血miR-152 DNA甲基化水平;采用SPSS 19.0统计软件对miR-152的表达水平与血脂水平进行相关性分析。结果 AS组患者血清总胆固醇(TC)、三酰甘油(TG)和低密度脂蛋白(LDL)显著高于对照组(均P<0.01),而高密度脂蛋白(HDL)则显著低于对照组(P<0.01);AS组患者外周血miR-152的表达水平较对照组显著降低(P<0.01),而miR-152启动子区DNA甲基化水平较对照组显著升高(P<0.01);相关性分析结果显示,miR-152的表达水平与TC、TG和LDL水平呈负相关,相关系数分别为-0.71、-0.69和-0.58;与HDL呈正相关,相关系数为0.61。结论AS患者外周血miR-152启动子区DNA甲基化程度升高使其表达水平降低,可能影响血液中血脂含量并最终导致AS的发生、发展。
Objective To investigate the mechanism of miR-152 expression alteration in peripheral blood of patients with atherosclerosis( AS) and its correlation with blood lipid levels. Methods Forty cases with AS( AS group) diagnosed by carotid Doppler ultrasonography between January 2015 to January 2015 were included in our hospital,and 40 health participants for physical examination( control group) were included at the same period as control. Biochemical analyzer was used to detect the blood lipid levels in both groups. Real-time fluorescent quantitative PCR( RT-qPCR) was used to detect the expression of miR-152 in peripheral blood. Nest type land type methylation specific PCR( nt-MSP)was used to detect the DNA methylation levels of miR-152 promoter region. SPSS19. 0 statistics software was used to analyze the correlation between miR-152 expression and blood lipid levels. Results The serum total cholesterol( TC),triglyceride( TG),low density lipoprotein( LDL) of AS patients were significantly higher than control group( P < 0. 01,P < 0. 01,P < 0. 01),with significantly lower high-density lipoprotein( HDL)( P < 0. 01). The expression of miR-152 of AS group was significantly lower than control group( P < 0. 01),and the DNA methylation level of miR-152 promoter region was significantly higher than control group( P < 0. 01). The expression level of miR-152 was significantly negatively correlated with TC,TG and LDL levels( OR = 0. 501 8,0. 428 0 and 0. 501 8,respectively); and positively correlated with HDL( OR = 0. 367 0). Conclusion The methylation of miR-152 promoter region of DNA induces the down-regulation of its expression,this may affect blood lipid levels and eventually lead to the development of AS.
Objective To investigate the mechanism of miR-152 expression alteration in peripheral blood of patients with atherosclerosis( AS) and its correlation with blood lipid levels. Methods Forty cases with AS( AS group) diagnosed by carotid Doppler ultrasonography between January 2015 to January 2015 were included in our hospital,and 40 health participants for physical examination( control group) were included at the same period as control. Biochemical analyzer was used to detect the blood lipid levels in both groups. Real-time fluorescent quantitative PCR( RT-qPCR) was used to detect the expression of miR-152 in peripheral blood. Nest type land type methylation specific PCR( nt-MSP)was used to detect the DNA methylation levels of miR-152 promoter region. SPSS19. 0 statistics software was used to analyze the correlation between miR-152 expression and blood lipid levels. Results The serum total cholesterol( TC),triglyceride( TG),low density lipoprotein( LDL) of AS patients were significantly higher than control group( P < 0. 01,P < 0. 01,P < 0. 01),with significantly lower high-density lipoprotein( HDL)( P < 0. 01). The expression of miR-152 of AS group was significantly lower than control group( P < 0. 01),and the DNA methylation level of miR-152 promoter region was significantly higher than control group( P < 0. 01). The expression level of miR-152 was significantly negatively correlated with TC,TG and LDL levels( OR = 0. 501 8,0. 428 0 and 0. 501 8,respectively); and positively correlated with HDL( OR = 0. 367 0). Conclusion The methylation of miR-152 promoter region of DNA induces the down-regulation of its expression,this may affect blood lipid levels and eventually lead to the development of AS.
引文
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[2]Tana C,Giamberardino MA,Cipollone F.microRNA profiling in atherosclerosis,diabetes and migraine[J].Ann Med,2016,49(2):93-105.
[3]Du HP,Li J,You SJ,et al.DNA methylation in cystathionine-γ-lyase(CSE)gene promoter induced by ox-LDL in macrophages and in apo E knockout mice[J].Biochem Biophys Res Commun,2016,469(3):776-782.
[4]Hai Z,Zuo W.Aberrant DNA methylation in the pathogenesis of atherosclerosis[J].Clin Chim Acta,2016,456:69-74.
[5]Ma SC,Zhang HP,Kong FQ,et al.Integration of gene expression and DNA methylation profiles provides a molecular subtype for risk assessment in atherosclerosis[J].Mol Med Rep,2016,13(6):4791-4799.
[6]Weber M,Baker MB,Moore JP,et al.MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and e NOS activity[J].Biochem Biophys Res Commun,2010,393(4):643-628.
[7]Zernecke A,Bidzhekov K,Noels H,et al.Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection[J].Sci Signal,2009,2(100):ra81.
[8]Fish JE,Santoro MM,Morton SU,et al.miR-126 regulates angiogenic signaling and vascular integrity[J].Dev Cell,2008,15(2):272-284.
[9]Harris TA,Yamakuchi M,Ferlito M,et al.MicroRNA-126 regulates endothelialexpression of vascular cell adhesion molecule 1[J].Proc Natl Acad Sci U S A,2008,105(5):1516-1521.
[10]Cipollone F,Felicioni L,Sarzani R,et al.A unique microRNA signature associated with plaque instability in humans[J].Stroke,2011,42(9):2556-2563.
[11]Liu X,Li J,Qin F,et al.miR-152 as a tumor suppressor microRNA:Target recognition and regulation in cancer[J].Oncol Lett,2016,11(6):3911-3916.
[12]Yu J,Qiu Y,Yang J,et al.DNMT1-PPARγpathway in macrophages regulates chronic inflammation and atherosclerosis development in mice[J].Sci Rep,2016,6:30053.
[13]Cao C,Zhang H,Zhao L,et al.miR-125b targets DNMT3b and mediates p53 DNA methylation involving in the vascular smooth muscle cells proliferation induced by homocysteine[J].Exp Cell Res,2016,347(1):95-104.
[14]Lv YC,Tang YY,Zhang P,et al.Histone Methyltransferase Enhancer of Zeste Homolog 2-Mediated ABCA1 Promoter DNA Methylation Contributes to the Progression of Atherosclerosis[J].PLo S One,2016,11(6):e0157265.
[15]Liu XL,Cao HX,Fan JG.MicroRNAs as biomarkers and regulators of nonalcoholic fatty liver disease[J].J Dig Dis,2016,17(11):708-715.