家族性高胆固醇血症患者接受低密度脂蛋白/脂蛋白(a) 单采治疗后循环miRNA的分析

Analysis of circulating miRNAs in patients with familial hypercholesterolaemia treated by LDL/Lp(a) apheresis.

作者信息

Dlouha Dana, Blaha Milan, Blaha Vladimir, Fatorova Ilona, Hubacek Jaroslav A, Stavek Petr, Lanska Vera, Parikova Alena, Pitha Jan

机构信息

Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

4th Department of Internal Medicine, Charles University School of Medicine and Teaching Hospital, Hradec Králové, Czech Republic.

出版信息

Atheroscler Suppl. 2017 Nov;30:128-134. doi: 10.1016/j.atherosclerosissup.2017.05.037. Epub 2017 Jun 1.

DOI:10.1016/j.atherosclerosissup.2017.05.037

PMID:29096828

Abstract

BACKGROUND

LDL/Lp(a) apheresis therapy is a well-established method of aggressively lowering LDL and Lp(a). Recently, miRNAs have been discussed as markers of vascular status including atherosclerosis. MiRNAs inhibit post-transcriptional processes through RNA duplex formation resulting in gene silencing or regulation of gene expression.

MATERIALS AND METHODS

We measured a profile of 175 plasma-circulating miRNAs using pre-defined Serum/Plasma Focus Human microRNA PCR Panels in pooled samples of 11 subjects with familial hypercholesterolaemia under long-term apheresis treatment. Subsequently we analysed expressions of ten pre-selected miRNAs potentially involved in lipid homeostasis in the same group of subjects. We compared plasma-circulating miRNA levels isolated from peripheral blood collected immediately before and after apheresis.

RESULTS

The greatest differences in plasma levels were found in miR-451a, miR-16, miR-19a/b, miR-223 and miR-185. In subsequent individual miRNA assay we detected a significant increase in miR-33b levels after apheresis (P < 0.05). Additionally, correlations between plasma lipids and miR-33a (P < 0.04) and miR-122 (P < 0.01) have been determined. Moreover, miR-122 levels in LDLR homozygotes were higher compared to heterozygotes after, but not before, apheresis treatment (P < 0.04).

CONCLUSIONS

LDL/Lp(a) apheresis has an impact on miRNAs associated with lipid homeostasis and vascular status.

摘要

背景

低密度脂蛋白/脂蛋白(a) 单采血浆置换疗法是一种有效降低低密度脂蛋白和脂蛋白(a) 的既定方法。最近，微小RNA（miRNA）已被作为包括动脉粥样硬化在内的血管状态标志物进行讨论。miRNA通过形成RNA双链体抑制转录后过程，从而导致基因沉默或调节基因表达。

材料与方法

我们使用预定义的血清/血浆聚焦人微小RNA PCR检测板，在11例接受长期单采血浆置换治疗的家族性高胆固醇血症患者的混合样本中，检测了175种血浆循环miRNA的谱。随后，我们分析了同一组受试者中10种预先选择的可能参与脂质稳态的miRNA的表达。我们比较了单采血浆置换前后立即采集的外周血中分离的血浆循环miRNA水平。

结果

血浆水平差异最大的是miR-451a、miR-16、miR-19a/b、miR-223和miR-185。在随后的单个miRNA检测中，我们检测到单采血浆置换后miR-33b水平显著升高（P < 0.05）。此外，还确定了血浆脂质与miR-33a（P < 0.04）和miR-122（P < 0.01）之间的相关性。此外，单采血浆置换治疗后，低密度脂蛋白受体纯合子中的miR-122水平高于杂合子，但治疗前并非如此（P < 0.04）。