O Sullivan John F, Neylon Antoinette, McGorrian Catherine, Blake Gavin J
Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Heart Research Institute, Newtown, NSW 2042, Australia.; Charles Perkins Centre, Johns Hopkins Drive, The University of Sydney, NSW 2006, Australia; Department of Cardiology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland..
Department of Cardiology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
Int J Cardiol. 2016 Dec 1;224:310-316. doi: 10.1016/j.ijcard.2016.09.016. Epub 2016 Sep 13.
MicroRNAs (miRNAs), small non-coding RNAs, have been implicated as regulators of all mediators of atherosclerosis, and some reports have suggested increased levels in coronary artery disease (CAD) and acute myocardial infarction (AMI). However, the potential of miRNAs as biomarkers or predictors of disease remains to be established.
We designed a study comprising 150 patients (50 Control, 50 Stable CAD, and 50 ST Elevation Myocardial Infarction (STEMI)), and measured plasma miRNAs in each. We then determined the ability of differential miRNAs, adjusting for Framingham Heart Study (FHS) risk factors, to discriminate between CAD vs Control, and STEMI vs Control.
Three miRNAs (miR15a-5p, miR16-5p, and miR93-5p) were significantly increased in Stable CAD vs Control groups and one (miR146a-5p) was significantly decreased in Stable CAD vs Control. One miRNA - miR499a-5p - was significantly increased in the STEMI group compared to Controls. After adjustment for FHS risk factors, miR93-5p levels remained an independent predictor of the presence of CAD (Odds Ratio [OR]=8.76, P=0.002). All 4 miRNAs improved discriminatory power for CAD over FHS alone in ROC analysis. Similarly, after adjustment for risk factors miR499-5p remained an independent predictor of STEMI (OR=3.03, P=0.001) and improved discriminatory power for STEMI in ROC analyses.
We identified 4 miRNAs that were differentially expressed among stable CAD and control patients, and 1 miRNA that was elevated in STEMI patients vs controls. MiR93-5p was the strongest predictor of CAD after adjustment for traditional risk factors, suggesting potential diagnostic utility.
微小RNA（miRNA）是一类小的非编码RNA，被认为是动脉粥样硬化所有介质的调节因子，一些报告表明其在冠状动脉疾病（CAD）和急性心肌梗死（AMI）中水平升高。然而，miRNA作为疾病生物标志物或预测指标的潜力仍有待确定。
我们设计了一项研究，纳入150例患者（50例对照、50例稳定型CAD和50例ST段抬高型心肌梗死（STEMI）），并测量了每组患者的血浆miRNA。然后，我们确定了差异miRNA在调整弗雷明汉心脏研究（FHS）风险因素后区分CAD与对照以及STEMI与对照的能力。
与对照组相比，稳定型CAD组中有3种miRNA（miR15a - 5p、miR16 - 5p和miR93 - 5p）显著升高，1种miRNA（miR146a - 5p）在稳定型CAD组与对照组相比显著降低。与对照组相比，STEMI组中有1种miRNA - miR499a - 5p显著升高。在调整FHS风险因素后，miR93 - 5p水平仍然是CAD存在的独立预测指标（优势比[OR]=8.76，P = 0.002）。在ROC分析中，所有这4种miRNA单独对CAD的鉴别能力均优于FHS。同样，在调整风险因素后，miR499 - 5p仍然是STEMI的独立预测指标（OR = 3.03，P = 0.001），并且在ROC分析中提高了对STEMI的鉴别能力。
我们鉴定出4种在稳定型CAD患者和对照患者中差异表达的miRNA，以及1种在STEMI患者与对照相比升高的miRNA。在调整传统风险因素后，miR93 - 5p是CAD最强的预测指标，提示其具有潜在的诊断价值。
