OSA患者动脉粥样硬化相关microRNA的表达谱探索分析

李坤; 陈志婷; 秦彦文; 魏永祥

doi:10.13201/j.issn.1001-1781.2019.04.005

OSA患者动脉粥样硬化相关microRNA的表达谱探索分析

- 1 首都医科大学附属北京安贞医院耳鼻咽喉头颈外科(北京, 100029);
- 2 北京市心肺血管疾病研究所
基金项目:
北京市医院管理局“登峰”计划专项经费资助(No:DFL20150602)

国家自然科学基金资助项目(No:81870335)

详细信息

通讯作者: 魏永祥,E-mail:anzhenent@163.com

中图分类号: R563.8

收稿日期: 2019-01-30

Expression profiles of microRNA related to atherosclerosis in patients with OSA

- 1 Department of Otolaryngology Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China;
- 2 Beijing Institute of Heart Lung and Blood Vessel Diseases

More Information

Corresponding author: WEI Yongxiang, E-mail: anzhenent@163.com

Received Date: 30 January 2019

摘要

摘要: 目的:研究OSA患者动脉粥样硬化(AS)相关血清microRNA(miRNA)的表达。方法:筛选116例受试者,包括对照组(n=24)、OSA组(n=32)、AS合并OSA组(n=32)和AS组(n=28)。对受试者进行qRTPCR分析miRNA表达谱。利用Spearman分析相关参数。结果:与对照组相比,OSA组、AS合并OSA组和AS组的miRNA-148a-5p、miRNA-378c、miRNA-127-3p和miRNA-365a-3p表达上调;AS组的miRNA-134-5p表达上调,AS合并OSA组的miRNA-365a-3p高于OSA组。AS相关的miRNA,包括miRNA-148a-5p、miRNA-378c、miRNA-127-3p、miRNA-134-5p和miRNA-365a-3p均与颈动脉内膜中层厚度相关。结论:表达上调的miRNA-148a-5p、miRNA-365a-3p、miRNA-378c和miRNA-127-3p可能是OSA患者发生AS的早期预警标志。
- 动脉粥样硬化 /
- 睡眠呼吸暂停 /
- 阻塞性 /
- microRNA
Abstract: Objective: Recent studies have demonstrated that obstructive sleep apnoea(OSA)may lead to atherosclerosis(AS),but the underlying mechanism remains unclear.MicroRNA(miRNA)may be involved in the gene regulation of AS and also in the occurrence and progression of OSA.The purpose of our study was to investigate the expression of atherosclerosis-related serum miRNAs in OSA patients.Method: We screened 116 participants including normal controls(n=24),OSA alone(n=32),OSA patients with AS(n=32),and patients with AS but without OSA(n=28).qRT-PCR to analyze the microRNA profile was performed in these subjects.Clinical and blood test with lipid parameters were analysed using Spearman correlations.Result: Compared to normal controls,miRNA-148 a-5 p,miRNA-378 c,miRNA-127-3 p and miRNA-365 a-3 p were upregulated in the OSA,OSA-AS,and AS groups;miRNA-134-5 p was only upregulated in the AS group,miRNA-365 a-3 p in the OSA-AS group was higher than that in the OSA alone group.The circulating atherosclerosis-related miRNAs,including miRNA-148 a-5 p,miRNA-378 c,miRNA-127-3 p,miRNA-134-5 p and miRNA-365 a-3 p all correlated with the carotid intima-media thickness.Conclusion: Upregulation of miRNA-148 a-5 p,miRNA-365 a-3 p,miRNA-378 c,miRNA-127-3 p may be an early warning marker of atherosclerosis in OSA patients.
- atherosclerosis /
- sleep apnoea /
- obstructive /
- microRNA

HTML全文

参考文献(27)

[1]	FRANKLIN K A,LINDBERG E.Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea[J].J Thorac Dis,2015,7:1311-1322.
[2]	PEPPARD P E,YOUNG T,ARNET J H,et al.Increased prevalence of sleep-disordered breathing in adults[J].Am J Pidemiol,2013,177:1006-1014.
[3]	YAGGI H K,CONCATO J,KERNAN W N,et al.Obstructive sleep apnea as a risk factor for stroke and death[J].New England J Med,2005,353:2034-2041.
[4]	MARIN J M,CARRIZO S J,VICENTE E,et al.Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure:an observational study[J].Lancet,2005,365:1046-1053.
[5]	PEKER Y,HEDNER J,NORUM J,et al.Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea:a 7-year follow-up[J].Am J Respire Crit Care Med,2002,166:159-165.
[6]	GOPALAKRISHNAN P,TAK T.Obstructive sleep apnea and cardiovascular disease[J].Cardiol Rev,2011,19:279-290.
[7]	BRADLEY T D,FLORAS J S.Obstructive sleep apnoea and its cardiovascular consequences[J].Lancet,2009,373:82-93.
[8]	BARTEL D P.MicroRNAs:genomics,biogenesis,mechanism,and function[J].Cell,2004,116:281-297.
[9]	KROL J,LOEDIGE I,FILIPOWICZ W.The widespread regulation of microRNA biogenesis,function and decay[J].Nature Rev Genet,2010,11:597-610.
[10]	BARTEL D P.MicroRNAs:target recognition and regulatory functions[J].Cell,2009,136:215-233.
[11]	GUO H,INGOLIA N T,WEISSMAN J S,et al.Mammalian microRNAs predominantly act to decrease target mRNA levels[J].Nature,2010,466:835-840.
[12]	VALENCIA-SANCHEZ M A,LIU J,HANNON G J.Control of translation and mRNA degradation by miR-NAs and siRNAs[J].Gene Dev,2006,20:515-524.
[13]	FRIEDMAN R C,FARH K K,BURGE C B,et al.Most mammalian mRNAs are conserved targets of microRNAs[J].Genome Res,2009,19:92-105.
[14]	LI T,CAO H,ZHUANG J.Identification of miR-130a,miR-27band miR-210as serum biomarkers for atherosclerosis obliterans[J].Clin Chim Acta,2011,412:66-70.
[15]	BORHANI N O,MERCURI M,BORHANI P A,et al.Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study(MIDAS).A randomized controlled trial[J].JAMA,1996,276:785-791.
[16]	DORIA A,SHOENFELD Y,WU R,et al.Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus[J].Ann Rheumat Dis,2003,62:1071-1077.
[17]	KROH E M,PARKIN R K,MITCHELL P S,et al.Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR[J].Methods,2010,50:298-301.
[18]	RANE S,HE M,SAYED D,et al.Downregulation of miR-199aderepresses hypoxia-inducible factor-1alpha and Sirtuin 1and recapitulates hypoxia preconditioning in cardiac myocytes[J].Circ Res,2009,104:879-886.
[19]	PRICE N L,RAMIREZ C M,FERNANDEZ-HER-NANDO C.Relevance of microRNA in metabolic diseases[J].Crit Rev Clin Lab Sci,2014,51:305-320.
[20]	CHAMI H A,RESNICK H E,QUAN S F,et al.Association of incident cardiovascular disease with progression of sleep-disordered breathing[J].Circulation,2011,123:1280-1286.
[21]	TURMEL J,SERIES F,BOULET L P,et al.Relationship between atherosclerosis and the sleep apnea syndrome:an intravascular ultrasound study[J].Int JCardiol,2009,132:203-209.
[22]	ANKER S D,VON HAEHLING S,GERMANY R.Sleep-disordered breathing and cardiovascular disease[J].Indian Heart J,2016,68:S69-76.
[23]	JUN J,REINKE C,BEDJA D,et al.Effect of intermittent hypoxia on atherosclerosis in apolipoprotein E-deficient mice[J].Atherosclerosis,2010,209:381-386.
[24]	KIM M H,HAM O,LEE S Y,et al.MicroRNA-365inhibits the proliferation of vascular smooth muscle cells by targeting cyclin D1[J].J Cell Biochem,2014,115:1752-1761.
[25]	QIN B,XIAO B,LIANG D,et al.MicroRNAs expression in ox-LDL treated HUVECs:miR-365modulates apoptosis and Bcl-2expression[J].Biochem Biophys Res Commun,2011,410:127-133.
[26]	NAPOLI C,QUEHENBERGER O,DE NIGRIS F,et al.Mildly oxidized low density lipoprotein activates multiple apoptotic signaling pathways in human coronary cells[J].FASEB J,2000,14:1996-2007.
[27]	GOEDEKE L,ROTLLAN N,CANFRAN-DUQUEA,et al.MicroRNA-148aregulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels[J].Nature Med,2015,21:1280-1289.