Laboratory of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
PLoS One. 2013 Nov 15;8(11):e80345. doi: 10.1371/journal.pone.0080345. eCollection 2013.
We examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable (SA) and Unstable (UA) angina.
An exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated.
Out of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA.
This work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients.
我们研究了冠心病（CAD）患者与匹配对照者血浆中循环 miRNA 表达谱，旨在确定稳定（SA）和不稳定（UA）心绞痛的新型鉴别生物标志物。
使用 TaqMan microRNA Arrays 对一组 SA 和 UA 患者和对照供体进行了血浆表达谱的探索性分析。通过 qRT-PCR 进行了筛选确认和表达分析：所有发现失调的 miRNA 均在肌钙蛋白阴性的 UA（n=19）和 SA（n=34）患者以及匹配的性别、年龄和心血管危险因素的对照受试者（n=20）的血浆中进行了检测。此外，还研究了 14 种已知与 CAD 相关的 miRNA 的表达。
在 178 种一致检测到的血浆样本 miRNA 中，有 3 种与对照组相比，在 CAD 时呈阳性调节：miR-337-5p、miR-433 和 miR-485-3p。此外，miR-1、-122、-126、-133a、-133b 和 miR-199a 在 UA 和 SA 患者中均呈阳性调节，而 miR-337-5p 和 miR-145 仅在 SA 或 UA 患者中呈阳性调节。ROC 曲线分析显示，miR-1、-126 和 -483-5p 在 SA 中，miR-1、-126 和 -133a 在 UA 患者中分别对对照的诊断具有良好的潜力（AUC≥0.85）。在比较 SA 与 UA 患者时，没有观察到有区别的 AUC 值。层次聚类分析显示，在 UA 中 miR-1、-133a 和 -126 的组合以及在 SA 中 miR-1、-126 和 -485-3p 的组合可以以≥87%的效率正确地将患者与对照者分类。没有 miRNA 的组合能够可靠地区分 UA 患者与 SA 患者。
这项工作表明，特定的血浆 miRNA 特征有可能准确地区分有血管造影记录的 CAD 患者与匹配的对照者。我们未能确定一种能够区分 SA 与 UA 患者的血浆 miRNA 表达模式。
