Non-invasive diagnosis of early-onset coronary artery disease based on cell type-specific gene expression analyses

• Published in: Biomedicine & pharmacotherapy Vol. 108; pp. 1115 - 1122
• Main Authors: Ziaee, Shayan, Boroumand, Mohammad Ali, Salehi, Rasoul, Sadeghian, Saeed, Hosseindokht, Maryam, Sharifi, Mohammadreza
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-12-2018
• Subjects: Adult; Age of Onset; Base Sequence; Biomarkers - metabolism; CD markers; Coronary Artery Disease - diagnosis; Coronary Artery Disease - genetics; Early-onset coronary artery disease; Female; Gene Expression Regulation; Humans; Lipopolysaccharide Receptors - genetics; Lipopolysaccharide Receptors - metabolism; Logistic Models; Long non-coding RNA SENCR; Male; Middle Aged; Multivariate Analysis; Reproducibility of Results; Risk Factors; Risk score; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Severity of Illness Index; Single-cell expression analysis; Single-cell expression analysis; Risk score; CD markers; Early-onset coronary artery disease; Long non-coding RNA SENCR
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.09.134

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•A scoring model was developed based on clinical and cell specific molecular markers.•This model was evaluated for early diagnosis of Early onset coronary artery disease.•Computational analysis predicted an interaction between lncRNA SENCR and CD14 mRNA.•Bimodal variation of SENCR in CEC and monocyte suggests its cell-specific functions.•Circulating endothelial cells can reflect molecular variation in vascular endothelium.
A non-invasive diagnostic method based on biomarkers related to endothelial and mononuclear cell dysfunction can provide opportunities for screening and early treatment of atherosclerosis. This study aimed to construct a risk scoring model based on clinical risk factors and molecular markers (lncRNA SENCR and CD markers) at single-cell level for early diagnosis of early-onset coronary artery disease (EOCAD). A single-cell expression analysis was performed on peripheral blood mononuclear cell subsets derived from 253 young individuals (Males ≤45 and Females ≤55 years old) in two training and validation sets using FISH-Flow assay. Concurrent quantifications of intracellular SENCR and surface/intracellular CD31, CD146, CD45 and CD14 in mononuclear cell fractions (Circulating endothelial cell, Monocyte and Lymphocyte) showed a significant reduction in intra-CEC SENCR, increased in intra-monocyte SENCR and also increased surface/intracellular CD146 and CD14 in patients with EOCAD as compared to the controls. Altered biomarkers were combined together as a risk scoring model. The ROC curve analysis on the combination model showed a high-performance in the distinction of our patients with EOCAD and healthy controls. A positive correlation between SENCR and CD14 in monocytes led us to find a binding site corresponding to SENCR and CD14 mRNA interaction. Our study suggested that combination of our molecular and clinical factors can be benefit to early diagnosis of EOCAD. CECs in peripheral blood as the novel approach could reflect molecular alteration in vascular endothelium. Bimodal variation in intracellular SENCR at the single-cell transcriptional level suggests that SENCR has cell-specific function(s) in its epigenetic gene regulation mechanisms.