Research & Development, Nour Heart, Inc., Vienna, VA 22180, USA.
Department of Surgery, UConn Health, School of Medicine, and Cell & Molecular Tissue Engineering, LLC, Farmington, CT 06032, USA.
Biomolecules. 2021 Feb 28;11(3):368. doi: 10.3390/biom11030368.
Currently, no blood biomarkers exist that can diagnose unstable angina (UA) patients. Nourin is an early inflammatory mediator rapidly released within 5 min by reversible ischemic myocardium, and if ischemia persists, it is also released by necrosis. Nourin is elevated in acute coronary syndrome (ACS) patients but not in symptomatic noncardiac and healthy subjects. Recently, circulating microRNAs (miRNAs) have been established as markers of disease, including cardiac injury and inflammation.
To profile and validate the potential diagnostic value of Nourin-dependent (marker of cell damage) and (marker of inflammation) as early biomarkers in suspected UA patients and to investigate the association of their target and regulating genes.
Using Nourin amino acid sequence, an integrated bioinformatics analysis was conducted. Analysis indicated that Nourin is a direct target for and in myocardial ischemic injury. Two linked molecular networks of lncRNA/miRNAs/mRNAs were also retrieved, including and //. Gene expression profiling was assessed in serum samples collected at presentation to an emergency department (ED) from: (1) UA patients ( = 30) (confirmed by invasive coronary angiography with stenosis greater than 50% and troponin level below the clinical decision limit); (2) patients with acute ST elevation myocardial infarction (STEMI) ( = 16) (confirmed by persistent ST-segment changes and elevated troponin level); and 3) healthy subjects ( = 16).
Gene expression profiles showed that and were significantly upregulated by 1382-fold and 192-fold in UA compared to healthy, and by 2.5-fold and 4.6-fold in STEMI compared to UA, respectively. Healthy subjects showed minimal expression profile. Receiver operator characteristics (ROC) analysis revealed that the two miRNAs were sensitive and specific biomarkers for assessment of UA and STEMI patients. Additionally, Spearman's correlation analysis revealed a significant association of miRNAs with the associated mRNA targets and the regulating lncRNA.
Nourin-dependent gene expression of and are novel blood-based biomarkers that can diagnose UA and STEMI patients at presentation and stratify severity of myocardial ischemia, with higher expression in STEMI compared to UA. Early diagnosis of suspected UA patients using the novel Nourin biomarkers is key for initiating guideline-based therapy that improves patients' health outcomes.
目前，尚无血液生物标志物可用于诊断不稳定型心绞痛（UA）患者。Nourin 是一种早期炎症介质，可在可逆性缺血心肌 5 分钟内迅速释放，如果缺血持续存在，也可由坏死释放。Nourin 在急性冠脉综合征（ACS）患者中升高，但在有症状的非心脏和健康受试者中不升高。最近，循环 microRNAs（miRNAs）已被确立为疾病的标志物，包括心脏损伤和炎症。
分析和验证 Nourin 依赖性（细胞损伤标志物）和（炎症标志物）作为疑似 UA 患者早期生物标志物的潜在诊断价值，并研究其靶基因和调节基因的相关性。
使用 Nourin 氨基酸序列进行综合生物信息学分析。分析表明，Nourin 是心肌缺血损伤中 miRNA 和 miRNA 的直接靶点。还检索到两个连接的长链非编码 RNA/miRNAs/mRNAs 分子网络，包括//和//。评估了从急诊科就诊的患者的血清样本中的基因表达谱：（1）UA 患者（n=30）（通过狭窄程度大于 50%的有创冠状动脉造影和低于临床决策限值的肌钙蛋白水平证实）；（2）急性 ST 段抬高型心肌梗死（STEMI）患者（n=16）（通过持续 ST 段变化和升高的肌钙蛋白水平证实）；和 3）健康受试者（n=16）。
基因表达谱显示，与健康对照组相比，UA 患者的和分别上调了 1382 倍和 192 倍，与 STEMI 相比，分别上调了 2.5 倍和 4.6 倍。健康对照组显示最小的表达谱。受试者工作特征（ROC）分析表明，这两种 miRNA 是评估 UA 和 STEMI 患者的敏感和特异的生物标志物。此外，Spearman 相关分析显示，miRNA 与相关 mRNA 靶标和调节 lncRNA 之间存在显著关联。
Nourin 依赖性基因表达的和是新型血液生物标志物，可在就诊时诊断 UA 和 STEMI 患者，并对心肌缺血的严重程度进行分层，与 STEMI 相比，STEMI 患者的表达更高。使用新型 Nourin 生物标志物对疑似 UA 患者进行早期诊断是启动基于指南的治疗的关键，可改善患者的健康结局。
