摘要
目的 探讨非瓣膜病心房颤动（房颤）患者血清小分子RNA（miRNA）全基因组表达差异及其可能的调控作用和早期预警价值.方法 15例房颤患者,分为阵发性、持续性和永久性房颤组,每组5例,对照组5例健康人.射频消融术前和术中分别取外周血和冠状窦血,提取血浆总RNA,使用microRNA芯片（microRNA v 18.0）进行全基因组miRNA表达谱微阵列分析,Volcano Plot法获得差异表达niRNAs,并用tMEV软件进行聚类分析,以及通过mirbase、miranda、targetscan数据库进行靶基因分析,并进行RT-PCR的差异表达验证.结果 房颤组冠状窦血与外周血比较有14个miRNAs表达差异显著,其中6个表达上调：即miR-1266、miR-4279、miR-4787-5p、miR-4666a-3p、kshv-miR-K12-6-3p和miR-3150a-5p,8个表达下调：即miR-892a、miR-3149 、miR-3171、miR-3664-5p、miR-3591-3p、miR-4423-5p、miR-4473和miR-574-3p.其中,miR-1266在阵发性、持续性和永久性房颤组均明显升高,而miR-3171则显著降低.房颤组与对照组外周血及冠状窦血比较miRNAs表达也有明显差异.结论 房颤患者冠状窦血与外周血比较miRNAs表达均有显著差异,而冠状窦血miRNAs更能反映心脏的代谢与调控状况;血清miR-3171、miR-892a、miR-3149在房颤发生发展早期出现且持续表达差异,有可能成为早期预警诊断的标志物;miR-1266、miR-4279、miR-4666a-3p有可能成为未来治疗房颤的干预靶点。
Objective To investigate the expression profiles of miRNAs in coronary sinus circulating, regulation mechanism and the value of earlier diagnosis of miRNAs in patients with atrial fibrillation （AF） of non- valvular heart disease. Methods The total 15 patients were divided into 4 groups： paroxysmal, persistent and per- manent atrial fibrillation patient＇s groups, each group contained 5 patients, while the control group 5 normal vol- unteers. The peripheral blood（PB） and coronary sinus blood（CSB） were taken from patients before and during the operation of AF radiofrequency ablation, the total RNA was extracted and hybridized with the microRNA chips （microRNA v 18.0）, the microarray analysis of expression profile, differential expression of miRNA and clustering analysis in whole genome were made with Volcano Plot and tMEV software respectively. The target gene analysis of miRNAs was research through the database of Mirhase, Miranda and Targetscan. Results There were 14 miRNAs different expression in CSB group compared with in PB group significantly, 6 was upregulation： miR-1266, miR- 4279, miR-4787-5p, miR-4666a-3p, kshv-miR-K12-6-3p and miR-3150a-5p, and 8 downregulation： miR- 892a, miR-3149, miR-3171, miR-3664-5p, miR-3591-3p, miR-4423-5p, miR-4473 and miR-574-3p. Among them, the expression of miR-1266 was increased, but the miR-3171 decreased dramatically whatever in paroxysmal, persistent and permanent atrial fibrillation groups. Also, the different expression of miRNAs in CSB group of AF patients compared with in PB group of normal control persons was shown significantly. Conclusion Compared with PB, the expression of miRNAs in CSB in AF patients themselves group was equal different markedly,which may indicate the miRNAs in CSB can better reflect the real metabolism and regulation status of myocardium in AF condition. The miR-3171, miR-892a and miR-3149 in plasma may be used as biomarker in earlier diagnosis of AF because their expression was increased or decreased respectively from early to end stage of AF continuously; miR-1266, miR-4279, miR-4666a-3p may be served as potential intervening targets of AF in the future.
出处
《中国心血管病研究》
CAS
2014年第11期995-1000,1053,共7页
Chinese Journal of Cardiovascular Research
关键词
心房颤动
基因调控
早期诊断
Atrial fibrillation
miRNA
Gene regulation
Earlier diagnosis
