Abstract
We aimed to investigate differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in atherosclerosis and validate the expression of lncRNAs and co-expressed target genes in proliferation and migration models of human coronary artery smooth muscle cells (HCASMCs). Ten coronary artery specimens from a subject who died from a heart attack were employed. The pathological analysis was analyzed by hematoxylin and eosin (H&E) staining, and the lncRNAs and mRNAs were identified by RNA sequencing. Bioinformatic analyses were performed to predict possible mechanisms. The proliferation and migration of HCASMCs were induced with oxidized low-density lipoprotein (ox-LDL). Differentially expressed lncRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). In this study, 68 lncRNAs and 222 mRNAs were identified differentially expressed in atherosclerosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the Fanconi anemia pathway may be involved in atherosclerosis. GON4L was found to be the co-localized target gene of LNC_000439, and 14 genes had high correlations with the expression of seven lncRNAs. In addition, nine lncRNA–miRNA–mRNA networks were constructed, and 53 co-expressed gene modules were detected with weighted gene co-expression network analysis (WGCNA). LNC_000684, LNC_001046, LNC_001333, LNC_001538, and LNC_002115 were downregulated, while LNC_002936 was upregulated in proliferation and migration models of HCASMCs. In total, six co-expressed mRNAs were upregulated in HCASMCs. This study suggests that the differentially expressed lncRNAs identified by RNA sequencing and validated in smooth muscle cells may be a target for regulating HCASMC proliferation and migration in atherosclerosis, which will provide a new diagnostic basis and therapeutic target for the treatment of cardiovascular diseases.
Highlights
Coronary heart disease (CHD), known as coronary artery disease (CAD), is the leading cause of morbidity and mortality globally (Benjamin et al, 2018; Amrein et al, 2020)
The purpose of the present study was to provide a comprehensive survey of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in human coronary arteries and identify differentially expressed lncRNAs and mRNAs and possible regulatory pathways according to the histological classification of atherosclerotic lesions
We identified 68 lncRNAs and 222 mRNAs that were differentially expressed in the 10 coronary artery segment samples by RNA sequencing
Summary
Coronary heart disease (CHD), known as coronary artery disease (CAD), is the leading cause of morbidity and mortality globally (Benjamin et al, 2018; Amrein et al, 2020). Traditional risk factors for CAD include diabetes, hyperlipidemia, hypertension, obesity, smoking, and family history. Low-density lipoprotein cholesterol (LDL-C) has been recognized as one of the major risk factors for CAD, which typically develops because of atherosclerotic plaque buildup in the coronary arteries (Case and Waksman, 2020; Jin et al, 2020). In the pathological processes of atherosclerosis, cholesterol containing oxidized low-density lipoprotein (ox-LDL) accumulates in the arterial wall, which promotes the proliferation and migration of medial vascular smooth muscle cells (VSMCs) in the intima and the formation of foam cells (Orekhov et al, 2020). Aberrant proliferation and migration of VSMCs lead to vascular remodeling during vasculopathy and atherosclerosis (Zhang et al, 2020). The differentially expressed genes and molecular mechanisms of VSMCs participating in atherosclerosis are potential therapeutic targets
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