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六种循环 microRNAs 在急性冠脉综合征中的诊断和预后影响。

Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome.

机构信息

Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany.

出版信息

J Mol Cell Cardiol. 2011 Nov;51(5):872-5. doi: 10.1016/j.yjmcc.2011.07.011. Epub 2011 Jul 23.

Abstract

Circulating microRNAs may have diagnostic potential in acute coronary syndrome (ACS). Previous studies, however, were based on low patient numbers and could not assess the relation of microRNAs to clinical characteristics and their potential prognostic value. We thus assessed the diagnostic and prognostic value of cardiomyocyte-enriched microRNAs in the context of clinical variables and a sensitive myonecrosis biomarker in a larger ACS cohort. MiR-1, miR-133a, miR-133b, miR-208a, miR-208b, and miR-499 concentrations were measured by quantitative reverse transcription PCR in plasma samples obtained on admission from 444 patients with ACS. High-sensitivity troponin T (hsTnT) was measured by immunoassay. Patients were followed for 6 months regarding all-cause mortality. In a multiple linear regression analysis that included clinical variables and hsTnT, miR-1, miR-133a, miR-133b, and miR-208b were independently associated with hsTnT levels (all P<0.001). Patients with myocardial infarction presented with higher levels of miR-1, miR-133a, and miR-208b compared with patients with unstable angina. However, all six investigated microRNAs showed a large overlap between patients with unstable angina or myocardial infarction. MiR-133a and miR-208b levels were significantly associated with the risk of death in univariate and age- and gender-adjusted analyses. Both microRNAs lost their independent association with outcome upon further adjustment for hsTnT. The present study tempers speculations about the potential usefulness of cardiomyocyte-enriched microRNAs as diagnostic or prognostic markers in ACS.

摘要

循环 microRNAs 可能在急性冠脉综合征 (ACS) 中有诊断潜力。然而,之前的研究基于低患者数量,无法评估 microRNAs 与临床特征的关系及其潜在的预后价值。因此,我们在更大的 ACS 队列中,根据临床变量和敏感的心肌坏死生物标志物评估了富含心肌细胞的 microRNAs 的诊断和预后价值。通过定量逆转录 PCR 在入院时从 444 名 ACS 患者的血浆样本中测量了 miR-1、miR-133a、miR-133b、miR-208a、miR-208b 和 miR-499 的浓度。通过免疫测定测量高敏肌钙蛋白 T (hsTnT)。对所有患者进行了 6 个月的随访,观察全因死亡率。在包含临床变量和 hsTnT 的多元线性回归分析中,miR-1、miR-133a、miR-133b 和 miR-208b 与 hsTnT 水平独立相关(均 P<0.001)。与不稳定型心绞痛患者相比,心肌梗死患者的 miR-1、miR-133a 和 miR-208b 水平更高。然而,不稳定型心绞痛或心肌梗死患者的所有六种研究 microRNAs 之间存在很大的重叠。miR-133a 和 miR-208b 水平在单变量和年龄及性别调整分析中与死亡风险显著相关。在进一步调整 hsTnT 后,这两种 microRNAs 失去了与结果的独立关联。本研究缓和了关于富含心肌细胞的 microRNAs 作为 ACS 诊断或预后标志物的潜在有用性的猜测。

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