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射频消融通过上调 microRNA-26a/b 的表达降低 SELF 的表达,从而治疗心房颤动。

Radiofrequency ablation reduces expression of SELF by upregulating the expression of microRNA-26a/b in the treatment of atrial fibrillation.

机构信息

Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, 12 Changjia Alley, Fucheng District, Mianyang, 621000, Sichuan, China.

出版信息

J Interv Card Electrophysiol. 2022 Dec;65(3):663-673. doi: 10.1007/s10840-022-01305-x. Epub 2022 Jul 21.

DOI:10.1007/s10840-022-01305-x
PMID:35864328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9726778/
Abstract

BACKGROUND

In this study, we aimed to investigate the role of miR-26a and miR-26b in the management of AF.

METHODS

Real-time PCR was carried out to determine plasma microRNA expression in AF patients pre- and post-radiofrequency ablation. The correlation between the expression of SELP and miR-26a/miR-26b was also studied using luciferase assays to establish a miR-26a/miR-26b/SELP signaling pathway.

RESULTS

The relative expression of SELP reached its peak in pre-ablation AF ( +) patients, while ablation treatment reduced the expression of SELP in AF ( +) patients. Similarly, AF pigs showed dysregulation of miR-26a/b and SELP, thus verifying the involvement of miR-26a/b and SELP in AF. Meanwhile, the regulatory association between SELP and miR-26a/b was also investigated, and the results showed that the presence of pre-miR-26a/b increased the levels of miR-26a/b and inhibited the mRNA/protein expression of SELP. Finally, using bioinformatic tools and luciferase assays, SELP mRNA was confirmed as the target of miR-26a/b, which affected the effect of AF ablation treatment.

CONCLUSIONS

RFA helped to restore circulating levels of miR-26, which were reduced in atrial fibrillation. Meanwhile, miR-26 is a potential cause for the elevated plasma levels of pro-thrombogenic SELP in that disease.

摘要

背景

本研究旨在探讨 miR-26a 和 miR-26b 在房颤管理中的作用。

方法

采用实时 PCR 法检测房颤患者射频消融术前后血浆 microRNA 表达,通过荧光素酶实验研究 SELP 与 miR-26a/miR-26b 的表达相关性,建立 miR-26a/miR-26b/SELP 信号通路。

结果

SELP 的相对表达在消融前房颤(+)患者中达到峰值,而消融治疗降低了房颤(+)患者 SELP 的表达。同样,房颤猪也表现出 miR-26a/b 和 SELP 的失调,从而验证了 miR-26a/b 和 SELP 参与房颤。同时,还研究了 SELP 和 miR-26a/b 之间的调控关系,结果表明前 miR-26a/b 的存在增加了 miR-26a/b 的水平,并抑制了 SELP 的 mRNA/蛋白表达。最后,通过生物信息学工具和荧光素酶实验证实 SELP mRNA 是 miR-26a/b 的靶标,影响房颤消融治疗的效果。

结论

RFA 有助于恢复房颤患者降低的循环 miR-26 水平。同时,miR-26 是导致该疾病中促血栓形成 SELP 血浆水平升高的潜在原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/87923de26d32/10840_2022_1305_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/915b76865863/10840_2022_1305_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/3c338120bac1/10840_2022_1305_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/c76a3765883c/10840_2022_1305_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/1c10723ebb95/10840_2022_1305_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/0dcb436411e9/10840_2022_1305_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/87923de26d32/10840_2022_1305_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/915b76865863/10840_2022_1305_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/3c338120bac1/10840_2022_1305_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/c76a3765883c/10840_2022_1305_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/1c10723ebb95/10840_2022_1305_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/0dcb436411e9/10840_2022_1305_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7589/9726778/87923de26d32/10840_2022_1305_Fig6_HTML.jpg

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