Nourin miRNAs: novel biomarkers highly expressed in unstable angina patients with normal ECG and negative hs-troponin and dropped post percutaneous coronary intervention

Abstract Background We recently reported that Nourin-dependent miR-137 and miR-106b can identify reversible myocardial ischemia in chest pain patients with a confirmed diagnosis of chronic stable chronic artery disease (CAD) and unstable angina (UA). These patients showed normal resting ECG and hs-cTnI below the clinical decision (<99th of URL). Normal, low-grade, baseline expression levels of Nourin miRNAs were detected in healthy subjects and in non-cardiac chest pain patients with hs-cTnI <99th URL. Purpose 1) To confirm the upregulation of Nourin miRNAs in chest pain patients with normal resting ECG and hs-cTnI < 99th URL, who are suspected of having UA; 2) whether Nourin miRNA expression levels change after relieving myocardial ischemia by PCI; and 3) whether there is an association between severity of chest of pain and Nourin miRNA expression levels prior to PCI. Methods This study enrolled 36 consecutive chest pain patients with normal resting ECGs and hs-cTnI <99th URL, from two large referral centers in Egypt. All enrolled patients had a single vessel disease with significant coronary stenosis (>70%) during diagnostic coronary angiography that was treated by PCI using standard techniques. The gene expression levels of miR-137 and miR-106b were measured in serum samples collected prior to PCI, as well as 12 hours and 24 hours post PCI. The angina class was evaluated at presentation, discharge, and after 4 weeks to verify angina relief. Results All patients (n=36) underwent successful PCI. Gene expression levels of miR-137 and miR-106b were significantly upregulated prior to PCI (mean ± SD: miR-137 = 355±150 and miR-106b =317±122) compared to healthy subjects (n=16) who showed minimal expression levels ranged from 0.615 to 1.05 (P <0.0001). Levels of both biomarkers dropped by 50% (12 hours) and 65% (24 hours) post PCI (P <0.05) (Figure 1). The expression levels of Nourin miRNAs did not associate with the Canadian class levels of angina severity. All patients were asymptomatic at discharge, while 84% remained asymptomatic after 4 weeks. Conclusions This study: 1) confirms that Nourin miR-137 and miR-106b can identify myocardial ischemia in patients presenting with unstable angina; 2) confirms that these two novel molecular biomarkers are elevated during myocardial ischemia, in the absence of myocardial injury; and 3) for the first time, we report a significant drop of Nourin miRNA expression levels post PCI, with myocardial ischemia relief.