miR-182在老年慢性心力衰竭病人循环中的表达及意义
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摘要
目的探讨micro RNA-182(miR-182)在老年慢性心力衰竭(心衰)诊断及判断预后中的价值。方法选取94例慢性心衰病人(心衰组),采用纽约心脏病学会(NYHA)标准进行心功能分级,其中NYHAⅡ级32例,Ⅲ级32例,Ⅳ级30例。另选取老年健康体检者31例作为对照组。应用逆转录-聚合酶链反应(RT-PCR)和电化学发光法分别检测2组病人循环中miR-182的表达情况和N末端脑钠肽前体(NT-proBNP)浓度,应用超声心动图测定左室射血分数(LVEF)评定病人心功能。结果心衰组外周血miR-182表达和NT-proBNP水平与对照组比较均明显升高,差异有统计学意义(P<0. 01)。Spearman直线相关分析显示,心衰组miR-182表达水平与年龄、肾功能、NT-proBNP浓度及心功能分级呈相关(r分别为0. 352、0. 461,P<0. 05),与LVEF呈负相关(r=-0. 246,P<0. 05)。通过绘制miR-182的受试者工作特征(ROC)曲线,miR-182曲线下面积(AUC)为0. 751,95%CI为0. 658～0. 843,差异有统计学意义(P<0. 01),诊断心衰的敏感性为40. 3%,特异性为93. 5%。结论 miR-182在诊断老年慢性心衰及判断预后中具有一定的价值,但也受年龄、肾功能的影响,作为心衰生物标记物并不优于NT-proBNP。
Objective To explore the value of microRNA 182( miR-182) in diagnosis and prognosis of chronic heart failure( CHF) in the elderly patients. Methods A total of 94 elderly patients with CHF( CHF group) were enrolled and assessed by NYHA grade,and 31 cases receiving health examination were selected as control group. The plasma levels of miR-182 and N-terminal pro-BNP( NTproBNP) in two groups were dectectd by reverse transcription-polymerase chain reaction( RT-PCR) and electrochemiluminescence immunoassay respectively. Meanwhile,the left ventricular ejection fraction( LVEF) was detected by electric cardiogram. Results The levels of miR-182 and NT-proBNP in the patients with CHF were significantly higher than those in control group( P< 0. 01). Spearman relation analysis showed significant positive correlation of the level of miR-182 with NT-proBNP and cardiac function grade,and negative correlation with LVEF. The receiver operator characteristic( ROC) curve showed that the area under the curve( AUC) was 0. 751( 95% CI: 0. 658-0. 843,P< 0. 01).Conclusions The plasma level of miR-182 shows certain value in predicting additional diagnostic and prognostic information for elderly patients with CHF,but it is not superior to NT-proBNP as a biomarker of heart failure.
Objective To explore the value of microRNA 182( miR-182) in diagnosis and prognosis of chronic heart failure( CHF) in the elderly patients. Methods A total of 94 elderly patients with CHF( CHF group) were enrolled and assessed by NYHA grade,and 31 cases receiving health examination were selected as control group. The plasma levels of miR-182 and N-terminal pro-BNP( NTproBNP) in two groups were dectectd by reverse transcription-polymerase chain reaction( RT-PCR) and electrochemiluminescence immunoassay respectively. Meanwhile,the left ventricular ejection fraction( LVEF) was detected by electric cardiogram. Results The levels of miR-182 and NT-proBNP in the patients with CHF were significantly higher than those in control group( P< 0. 01). Spearman relation analysis showed significant positive correlation of the level of miR-182 with NT-proBNP and cardiac function grade,and negative correlation with LVEF. The receiver operator characteristic( ROC) curve showed that the area under the curve( AUC) was 0. 751( 95% CI: 0. 658-0. 843,P< 0. 01).Conclusions The plasma level of miR-182 shows certain value in predicting additional diagnostic and prognostic information for elderly patients with CHF,but it is not superior to NT-proBNP as a biomarker of heart failure.
引文
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[2]Schneider M,Andersen DC,Silahtaroglu A,et al.Cellspecific detection of microRNA expression during cardiomyogenesis by combined in situ hybridization and immunohistoche-mistry[J].J Mol Histol,2011,42(4):289-299.
[3]Kuwabara Y,Ono K,Horie T,Nishi H,et al.Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage[J].Circ Cardiovasc Genet,2011,4(4):446-454.
[4]Tortes M,Moayedi S.Evaluation of the acutely dyspneic elderly patient[J].Clin Geriatr Med,2007,23(2):307-325.
[5]Schulte C,Westermann D,Blankenberg S,et al.Diagnostic and prognostic value of circulating microRNAs in heart failure with preserved and reduced ejection fraction[J].World J Cardiol,2015,7(12):843-860.
[6]Zhang J,Xing Q,Zhou X,et al.Circulating miRNA\-21 is a promising biomarker for heart failure[J].Mol Med Rep,2017,16(5):7766-7774.
[7]Endo K,Naito Y,Ji x,et al.MicroRNA 210 as a biomarker for congestive heart failure[J].Biol Pharm Bull,2013,36(1):48-54.
[8]Yancy CW,Jessup M,Bozkurt B,et al.2017ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart Failure:a report of the American college of cardiology/American heart association task force on clinical practice guidelines and the heart failure society of America[J].Circulation,2017,136(6):e137-161.
[9]糜涛,张存泰.老年人慢性心力衰竭[J].中华老年医学杂志,2016,35(3):236-238.
[10]Lagos-Quintana M,Rauhut R,Meyer J,et al.New micro RNAs from mouse and human[J].RNA,2003,9(2):175-179.
[11]Kim KM,Park SJ,Jung SH,et al.miR-182 is a negative regulator of osteoblast proliferation,differentiation,and skeletogenesis through targeting Fox O1[J].J Bone Miner Res,2012,27(8):1669-1679.
[12]Friedman LM,Dror AA,Mor E,et al.MicroRNAs are essential for development and function of inner ear hair cells in vertebrates[J].Proc Natl Acad Sci USA,2009,106(19):7915-7920.
[13]Wei Q,Lei R,Hu GH.Roles of miR-182 in sensory organ development and cancer[J].Thorac Cancer,2015,6(1):2-9.
[14]Zhang QH,Sun HM,Zheng RZ,et al.Meta-analysis of microRNA-183 family expression in human cancer studies comparing cancer tissues with noncancerous tissues[J].Gene,2013,527(1):26-32.
[15]Klein D,Misawa R,Bravo-Egana V,et al.MicroRNA expression in alpha and beta cells of human pancreatic islets[J].PLoS One,2013,8(1):e55064.
[16]Jeon TI,Esquejo RM,Roqueta-Rivera M,et al.An SREB-presponsive microRNA operon contributes to a regulatory loop for intracellular lipid homeostasis[J].Cell Metab,2013,18(1):51-61.
[17]孟哲颖,王玉,林艳端,等.微小RNA-182通过靶基因Racl调控高糖诱导的心肌细胞肥大[J].中华心血管病杂志,2015,43(7):619-624.
[18]Cakmak HA,Coskunpinar E,Ikitimur B,e tal.The prognostic value of circulating microRNAs in heart failure:preliminary results from a genome-wide expression study[J].JCardiovasc Med(Hagerstown),2015,16(6):431-437.