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扩张型心肌病中循环纤维化相关微小RNA(miR-21、miR-29、miR-30和miR-133a)的12个月动态变化及其与细胞外基质纤维化的关系

Twelve-month kinetics of circulating fibrosis-linked microRNAs (miR-21, miR-29, miR-30, and miR-133a) and the relationship with extracellular matrix fibrosis in dilated cardiomyopathy.

作者信息

Rubiś Paweł, Totoń-Żurańska Justyna, Kołton-Wróż Maria, Wołkow Paweł, Pitera Ewelina, Wiśniowska-Śmiałek Sylwia, Dziewięcka Ewa, Garlitski Ann, Podolec Piotr

机构信息

Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, Krakow, Poland.

Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Krakow, Poland.

出版信息

Arch Med Sci. 2019 Nov 18;18(2):480-488. doi: 10.5114/aoms.2019.89777. eCollection 2022.

Abstract

INTRODUCTION

A single measurement of any biomarker may not reflect its full biological meaning. The kinetics of fibrosis-linked microRNAs and their relationship with extracellular matrix (ECM) fibrosis in dilated cardiomyopathy (DCM) have not been explored.

MATERIAL AND METHODS

We evaluated 70 consecutive DCM patients (48 ±12.1 years, left ventricular ejection fraction 24.4 ±7.4%). All patients underwent right ventricular endomyocardial biopsy in order to quantify ECM fibrosis and measure collagen volume fraction (CVF). Circulating microRNAs (miR-21-5p, miR-29b, miR-30c-5p, and miR-133a-3p) were measured with quantitative polymerase chain reaction (PCR) at baseline and at 3 and 12 months.

RESULTS

Based on the biopsy results, two groups of patients were identified: with ( = 24, 34.3%) and without ( = 46, 65.7%) ECM fibrosis. Except for a single measurement of miR-29b at 3 months (DCM with fibrosis: 6.03 ±0.72 vs. DCM without fibrosis: 6.4 ±0.75 ΔCq; < 0.05), baseline, 3- and 12-month kinetics of microRNAs did not differ between the two groups. Moreover, 12-month microRNA kinetics did not differ in patients with new-onset DCM (duration < 6 months; = 35) and chronic DCM (> 6 months; = 35). Only miR-29 at 3 months correlated with CVF ( = -0.31; < 0.05), whereas other microRNAs did not correlate with CVF either at 3 or at 12 months.

CONCLUSIONS

Regardless of ECM fibrosis status or duration of the disease, 12-month patterns of circulating microRNAs are similar in DCM. Correlations between microRNAs, measured at 3 and 12 months, are lower than expected. In this study, regardless of the time point, circulating microRNAs were not able to differentiate between DCM patients with versus without fibrosis.

摘要

引言

任何生物标志物的单次测量可能无法反映其全部生物学意义。扩张型心肌病(DCM)中与纤维化相关的微小RNA的动力学及其与细胞外基质(ECM)纤维化的关系尚未得到研究。

材料与方法

我们评估了70例连续的DCM患者(48±12.1岁,左心室射血分数24.4±7.4%)。所有患者均接受右心室心内膜活检,以量化ECM纤维化并测量胶原容积分数(CVF)。在基线、3个月和12个月时,采用定量聚合酶链反应(PCR)检测循环微小RNA(miR-21-5p、miR-29b、miR-30c-5p和miR-133a-3p)。

结果

根据活检结果,将患者分为两组:有ECM纤维化组(n = 24,34.3%)和无ECM纤维化组(n = 46,65.7%)。除了在3个月时对miR-29b的单次测量(有纤维化的DCM:6.03±0.72 vs.无纤维化的DCM:6.4±0.75ΔCq;P < 0.05)外,两组之间微小RNA的基线、3个月和12个月动力学无差异。此外,新发DCM患者(病程<6个月;n = 35)和慢性DCM患者(>6个月;n = 35)的12个月微小RNA动力学无差异。仅3个月时的miR-29与CVF相关(r = -0.31;P < 0.05),而其他微小RNA在3个月或12个月时均与CVF无关。

结论

无论ECM纤维化状态或疾病持续时间如何,DCM患者循环微小RNA的12个月模式相似。在3个月和12个月时测量的微小RNA之间的相关性低于预期。在本研究中,无论时间点如何,循环微小RNA均无法区分有纤维化和无纤维化的DCM患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5e7/8924829/000d15dc9e2c/AMS-18-2-103805-g001.jpg

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