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

(2018) Non-invasive diagnosis of early-onset coronary artery disease based on cell type-specific gene expression analyses. Biomed Pharmacother. pp. 1115-1122. ISSN 1950-6007 (Electronic) 0753-3322 (Linking)

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Abstract

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.

Item Type: Article
Keywords: CD markers Early-onset coronary artery disease Long non-coding RNA SENCR Risk score Single-cell expression analysis
Divisions: Faculty of Medicine > Department of Basic Science > Department of Molecular Medicine and Genetics
Page Range: pp. 1115-1122
Journal or Publication Title: Biomed Pharmacother
Journal Index: Pubmed
Volume: 108
Identification Number: https://doi.org/10.1016/j.biopha.2018.09.134
ISSN: 1950-6007 (Electronic) 0753-3322 (Linking)
Depositing User: Zahra Otroj
URI: http://eprints.mui.ac.ir/id/eprint/8073

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