Role of lncRNAs in Remodeling of the Coronary Artery Plaques in Patients with Atherosclerosis

Abstract

Abstract Introduction Cardiovascular diseases (CVDs) are the leading cause of death worldwide according to World Health Organi zation (WHO) data. Atherosclerosis is considered as a chronic infammatory disease that develops in response to damage to the vascular intima-media layer in most cases. In recent years, epigenetic events have emerged as important players in the development and progression of CVDs. Since noncoding RNA (ncRNAs) are important regulators in the organization of the pathophysiological processes of the cardiovascular system, they have the potential to be used as therapeutic targets, diagnostic and prognostic biomarkers. In this study long noncoding RNA (lncRNA) and mRNA gene expression were com pared between coronary atherosclerotic plaques (CAP) and the internal mammary artery (IMA) which has the same genetic makeup and is exposed to the same environmental stress conditions with CAP in the same individual. Methods lncRNA and mRNA gene expressions were determined using the microarray in the samples. Microarray results were validated by RT-qPCR. Diferentially expressed genes (DEGs; lncRNAs and mRNAs) were determined by GeneSpring (Ver 3.0) [p values < 0.05 and fold change (FC) > 2]. DAVID bioinformatics program was used for Gene Ontology (GO) annotation and enrichment analyses of statistically signifcant genes between CAP and IMA tissue. Results and Conclusions In our study, 345 DEGs were found to be statistically signifcant (p < 0.05; FC > 2) between CAP and IMA. Of these, 65 were lncRNA and 280 were mRNA. Thirty-three lncRNAs were upregulated, while 32 lncRNAs were downregulated. Some of the important mRNAs are SPP1, CYP4B1, CHRDL1, MYOC, and ALKAL2, while some of the lncRNAs are LOC105377123, LINC01857, DIO3OS, LOC101928134, and KCNA3 between CAP and IMA tissue. We also identifed genes that correlated with statistically signifcant lncRNAs. The results of this study are expected to be an important source of data in the development of new genetically based drugs to prevent atherosclerotic plaque. In addition, the data obtained may contribute to the explanation of the epigenetic mechanisms that play a role in the pathological basis of the process that protects the IMA from atherosclerosis.