The Scripps Translational Science Institute, The Scripps Research Institute, Scripps Health, La Jolla, USA.
Ortho Clinical Diagnostics, Raritin, NJ, USA.
Sci Rep. 2017 Sep 25;7(1):12268. doi: 10.1038/s41598-017-12166-0.
Chest pain is a leading reason patients seek medical evaluation. While assays to detect myocyte death are used to diagnose a heart attack (acute myocardial infarction, AMI), there is no biomarker to indicate an impending cardiac event. Transcriptional patterns present in circulating endothelial cells (CEC) may provide a window into the plaque rupture process and identify a proximal biomarker for AMI. Thus, we aimed to identify a transcriptomic signature of AMI present in whole blood, but derived from CECs. Candidate genes indicative of AMI were nominated from microarray of enriched CEC samples, and then verified for detectability and predictive potential via qPCR in whole blood. This signature was validated in an independent cohort. Our findings suggest that a whole blood CEC-derived molecular signature identifies patients with AMI and sets the framework to potentially identify the earlier stages of an impending cardiac event when used in concert with clinical history and other diagnostics where conventional biomarkers indicative of myonecrosis remain undetected.
胸痛是患者寻求医学评估的主要原因。虽然检测肌细胞死亡的检测方法可用于诊断心脏病发作（急性心肌梗死，AMI），但尚无生物标志物可提示即将发生心脏事件。循环内皮细胞（CEC）中存在的转录模式可能提供斑块破裂过程的窗口，并确定 AMI 的近端生物标志物。因此，我们旨在鉴定存在于全血但源自 CEC 的 AMI 的转录组特征。从富集的 CEC 样本的微阵列中提名提示 AMI 的候选基因，然后通过 qPCR 在全血中验证其可检测性和预测潜力。该特征在独立队列中得到验证。我们的研究结果表明，源自全血 CEC 的分子特征可识别 AMI 患者，并为在与临床病史和其他诊断方法（其中常规生物标志物指示肌坏死仍未被检测到）联合使用时，确定即将发生心脏事件的早期阶段奠定了框架。
