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Whole blood transcriptome profile at hospital admission discriminates between patients with ST-segment elevation and non-ST-segment elevation acute myocardial infarction.
Scientific Reports ( IF 4.6 ) Pub Date : 2020-05-26 , DOI: 10.1038/s41598-020-65527-7
Mattia Chiesa 1 , Luca Piacentini 1 , Elisa Bono 1 , Valentina Milazzo 2 , Jeness Campodonico 2 , Giancarlo Marenzi 2 , Gualtiero I Colombo 1
Affiliation  

Whether ST-segment (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) should be regarded as distinct pathophysiological entities is a matter of debate. We tested the hypothesis that peripheral blood gene-expression profiles at presentation distinguish STEMI from NSTEMI. We performed a case-control study collecting whole-blood from 60 STEMI and 58 NSTEMI (defined according to the third universal definition of MI) consecutive patients on hospital admission. We used RNA-sequencing for the discovery phase, comparing 15 STEMI vs. 15 NSTEMI patients, matched for age, sex, and cardiovascular risk factors, and quantitative PCR in the remaining unmatched patients for validating top-significant genes. Gene-level differential expression analysis identified significant differences in the expression of 323 genes: 153 genes withstood correction for admission cardiac troponin I (cTnI), differentiating the two conditions independently of myocardial necrosis extent. Functional annotation analysis uncovered divergent modulation in leukocyte and platelet activation, cell migration, and mitochondrial respiratory processes. Linear regression analysis revealed gene expression patterns on admission predicting infarct size, as indexed by cTnI peak (R2 = 0.58–0.75). Our results unveil distinctive pathological traits for these two MI subtypes and provide insights into the early assessment of injury extent. This could translate into RNA-based disease-specific biomarkers for precision diagnosis and risk stratification.



中文翻译:

住院时的全血转录组谱可区分ST段抬高和非ST段抬高的急性心肌梗死患者。

是否应将ST段(STEMI)和非ST段抬高型心肌梗塞(NSTEMI)视为不同的病理生理实体,这尚有争议。我们检验了假设的外周血基因表达谱将STEMI与NSTEMI区分开。我们进行了一项病例对照研究,收集了入院时连续60例STEMI和58例NSTEMI(根据MI的第三个通用定义)的全血。我们将RNA测序用于发现阶段,比较了15 STEMI。15例NSTEMI患者,匹配了年龄,性别和心血管疾病危险因素,其余未匹配的患者中进行了定量PCR,以验证最重要的基因。基因水平差异表达分析确定了323个基因表达的显着差异:153个基因经受住了心脏肌钙蛋白I(cTnI)的校正,从而区分了两种情况,而与心肌坏死程度无关。功能注释分析发现白细胞和血小板活化,细胞迁移和线粒体呼吸过程中的发散调节。线性回归分析显示入院时的基因表达模式可预测梗死面积,以cTnI峰(R 2 = 0.58–0.75)。我们的结果揭示了这两种MI亚型的独特病理特征,并提供了对损伤程度的早期评估的见识。这可以转化为基于RNA的疾病特异性生物标记物,以进行精确诊断和风险分层。

更新日期:2020-05-26
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