RNA sequencing human monocytes

Aim: To improve risk stratification in patients with stable coronary artery disease (CAD), we aimed to identify genes in monocytes predictive of new ischemic events in patients with CAD and determine to what extent expression of these transcripts resembles expression in acute myocardial infarction (AMI). Results: COX10 and ZNF484 distinguished between AMI and the whole group of stable CAD patients with an accuracy of 90%. COX10 and ZNF484 together with MT-COI and WNK1 distinguished AMI patients from stable CAD patients with and without a new event with a sensitivity of 89% and a specificity of 98%. MT-COI and COX10 increased the accuracy for separating stable CAD patients with and without a new coronary event from 68 to 80% in addition to age, gender, BMI, diabetes, lipids, blood pressure and hs-CRP. Interestingly, expression of MT-COI, COX10 and WNK1 (but not ZNF484) in PBMCs paired with that in monocytes; COX10 in whole blood was similar to that in monocytes. Conclusions: This work showed that COX10 and ZNF484, eventually combined with MT-COI and WNK1 have the potential to accurately discriminate between AMI and stable CAD patients, and may improve the risk assessment of stable CAD patients. We included 19 AMI and 66 CAD patients which were stable at time of blood sampling; 24 of the latter developed a new coronary event: sudden death, new AMI, stroke or urgent coronary revascularization. Circulating CD14+ monocytes were isolated with magnetic beads. Exploratory RNA sequence analysis (36 individual samples; 11 in group 1 i.e CAD pateints without new event; 13 patients in group 2 i.e. CAD patients with new event; 12 patients in group 3 i.e. AMI patients. Expressions were validated with qPCR in monocytes (85 patients).