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心外膜脂肪组织厚度及微小RNA表达改变与猝死受害者的冠心病相关。

Thickness and an Altered miRNA Expression in the Epicardial Adipose Tissue Is Associated With Coronary Heart Disease in Sudden Death Victims.

作者信息

Marí-Alexandre Josep, Barceló-Molina Moises, Sanz-Sánchez Jorge, Molina Pilar, Sancho Jennifer, Abellán Yolanda, Santaolaria-Ayora María Luisa, Giner Juan, Martínez-Dolz Luis, Estelles Amparo, Braza-Boïls Aitana, Zorio Esther

机构信息

Unidad de Cardiopatías Familiares, Muerte Súbita y Mecanismos de Enfermedad (CaFaMuSMe), Instituto de Investigación Sanitaria La Fe, Valencia, Spain.

Servicio de Cardiología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.

出版信息

Rev Esp Cardiol (Engl Ed). 2019 Jan;72(1):30-39. doi: 10.1016/j.rec.2017.12.007. Epub 2018 Feb 10.

DOI:10.1016/j.rec.2017.12.007
PMID:29439878
Abstract

INTRODUCTION AND OBJECTIVES

An increased epicardial adipose tissue (EAT) thickness has become a new risk factor for coronary heart disease (CHD). We aimed to study the role of EAT dysfunction as a CHD marker by focusing on its thickness and microRNA (miRNA) expression profile, and the potential factors possibly influencing them.

METHODS

One hundred and fifty-five CHD sudden cardiac death victims and 84 non-CHD-sudden death controls were prospectively enrolled at autopsy. A representative subset underwent EAT thickness measurements and EAT miRNA expression profiling.

RESULTS

Epicardial adipose tissue thickness was increased and allowed an accurate diagnosis of patient status (among other measurements, EAT score area under the curve 0.718, P < .001). Epicardial adipose tissue from patients showed 14 up- and 14 down-regulated miRNAs and miR-34a-3p, -34a-5p, -124-3p, -125a-5p, 628-5p, -1303 and -4286 were validated by quantitative real-time polymerase chain reaction. Patients exhibited higher EAT levels of miR-34a-3p and -34a-5p than controls (with a positive trend considering EAT from coronaries without stenosis, with stable stenosis and complicated plaques) and correlated with age only in controls. The mild positive correlation between liver and EAT miR-34a-5p levels in patients (r = 0.295, P = .020) dramatically increased in EAT from complicated plaques (r = 0.799, P = .017). Similar correlations were observed for high-sensitivity-C-reactive protein levels and miR-34a-5p levels both in EAT and liver extracts.

CONCLUSIONS

Increased age-independent levels of miR-34a-3p and -34a-5p characterize the EAT miRNA expression profile of CHD regardless of EAT thickness, anthropometric parameters, and the presence of underlying atherosclerotic plaques.

摘要

引言与目的

心外膜脂肪组织(EAT)厚度增加已成为冠心病(CHD)的一个新危险因素。我们旨在通过关注EAT厚度和微小RNA(miRNA)表达谱以及可能影响它们的潜在因素,研究EAT功能障碍作为CHD标志物的作用。

方法

前瞻性纳入155例CHD心脏性猝死受害者和84例非CHD猝死对照进行尸检。对一个代表性亚组进行EAT厚度测量和EAT miRNA表达谱分析。

结果

心外膜脂肪组织厚度增加,能够准确诊断患者状态(在其他测量中,EAT评分曲线下面积为0.718,P <.001)。患者的心外膜脂肪组织显示14种miRNA上调和14种miRNA下调,并且通过定量实时聚合酶链反应验证了miR-34a-3p、-34a-5p、-124-3p、-125a-5p、628-5p、-1303和-4286。患者的EAT中miR-34a-3p和-34a-5p水平高于对照(对于无狭窄、稳定狭窄和复杂斑块的冠状动脉的EAT,呈阳性趋势),并且仅在对照中与年龄相关。患者肝脏和EAT中miR-34a-5p水平之间的轻度正相关(r = 0.295,P = 0.020)在复杂斑块的EAT中显著增加(r = 0.799,P = 0.017)。在EAT和肝脏提取物中,高敏C反应蛋白水平和miR-34a-5p水平之间也观察到类似的相关性。

结论

无论EAT厚度、人体测量参数以及潜在动脉粥样硬化斑块的存在如何,年龄无关的miR-34a-3p和-34a-5p水平升高是CHD患者EAT miRNA表达谱的特征。

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