Cui Yuxia, Su Ying, Li Long, Zhao Sheng, Nan Jing, Yue Yunan, Yang Shuixiang
Department of Cardiology, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing 100038, China.
Department of Cardiology, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing 100038, China; Email:
Zhonghua Xin Xue Guan Bing Za Zhi. 2015 Dec;43(12):1051-6.
To observe the change of circulating microRNAs(miRNAs), regulatory mechanism in patients with atrial fibrillation (AF) before and after radiofrequency ablation (RFA).
From January 2011 to December 2013, peripheral blood samples were taken from 30 AF patients (10 paroxysmal, 10 persistent and 10 permanent AF) before and 3 months after RFA. The total RNA was extracted and hybridized with the miRNA chips, and the differential expression of miRNA and clustering analysis in whole genome were made with Volcano Plot and tMEV software respectively, and validated by real-time PCR. The target gene analysis of miRNAs was predicted through the Mirbase, Miranda and Targetscan databases. Results were compared with those from 10 healthy subjects (control group).
Compared with control group, the expressions of 25 miRNAs were down-regulated before RFA and up-regulated after RFA in AF group, while other 40 miRNAs expression changed in the opposite way; among them, the expressions of 7 miRNAs including miR-199a-3p/miR-199b-3p were down- regulated >1.5-fold before RFA and up-regulated>100-fold after RFA; oppositely, 6 miRNAs including miR-BART8-3p were up-regulated>1.5-fold before RFA and down-regulated>10-fold after RFA. Interestingly, 6 miRNAs including miR-30b-5p, which were involved in AF-related electrical and structural remodeling, were down-regulated>5-fold before RFA, but up-regulated>50-fold after RFA. Four miRNAs including miR-377-5p, which were involved in the regulation of CACNA1C ICaL channel protein, were different before and after RFA.
miRNAs regulate the occurrence and development of AF. RFA can change the expression of miRNAs in AF patients, which may be important for reversing the electrical and structural remodeling and maintaining sinus rhythm after RFA. miRNAs, such as miR-30b-5p, miR-377-5p and miR-199a-3p/miR-199b-3p etc., might become the target markers for early diagnosis and intervention of AF in future.
观察心房颤动(AF)患者射频消融(RFA)前后循环微小RNA(miRNA)的变化及其调控机制。
选取2011年1月至2013年12月期间30例AF患者(阵发性10例、持续性10例、永久性10例),分别于RFA术前及术后3个月采集外周血样本。提取总RNA并与miRNA芯片杂交,分别用火山图和tMEV软件对miRNA的差异表达及全基因组聚类分析,并用实时荧光定量PCR进行验证。通过Mirbase、Miranda和Targetscan数据库对miRNA的靶基因进行预测分析。将结果与10例健康受试者(对照组)进行比较。
与对照组相比,AF组25个miRNA在RFA术前表达下调,术后上调,另外40个miRNA表达变化情况相反;其中,包括miR-199a-3p/miR-199b-3p在内的7个miRNA在RFA术前表达下调>1.5倍,术后上调>100倍;相反,包括miR-BART8-3p在内的6个miRNA在RFA术前上调>1.5倍,术后下调>10倍。有趣的是,包括miR-30b-5p在内的6个参与AF相关电重构和结构重构的miRNA在RFA术前下调>5倍,但术后上调>50倍。包括miR-377-5p在内的4个参与调控CACNA1C ICaL通道蛋白的miRNA在RFA前后存在差异。
miRNA调控AF的发生发展。RFA可改变AF患者miRNA的表达,这可能对逆转电重构和结构重构以及RFA术后维持窦性心律具有重要意义。miR-30b-5p、miR-377-5p和miR-199a-3p/miR-199b-3p等miRNA可能成为未来AF早期诊断和干预的靶标标志物。