Abstract
Long noncoding (lnc)RNAs have been implicated in the development and progression of atherosclerosis. However, the expression and mechanism of action of lncRNAs in atherosclerosis are still unclear. We implemented microarray analysis in human advanced atherosclerotic plaques and normal arterial intimae to detect the lncRNA and mRNA expression profile. Gene Ontology functional enrichment and pathway analyses were applied to explore the potential functions and pathways involved in the pathogenesis of atherosclerosis. A total of 236 lncRNAs and 488 mRNAs were selected for further Ingenuity Pathway Analysis. Moreover, quantitative RT-PCR tests of most selected lncRNAs and mRNAs with high fold changes were consistent with the microarray data. We also performed ELISA to investigate the corresponding proteins levels of selected genes and showed that serum levels of SPP1, CD36, ATP6V0D2, CHI3L1, MYH11, and BDNF were differentially expressed in patients with coronary heart disease compared with healthy subjects. These proteins correlated with some biochemical parameters used in the diagnosis of cardiovascular diseases. Furthermore, receiver operating characteristic analysis showed a favorable diagnostic performance. The microarray profiling analysis and validation of differentially-expressed lncRNAs and mRNAs in atherosclerosis not only provide new insights into the pathogenesis of this disease but may also reveal new biomarkers for its diagnosis and treatment.
Highlights
Atherosclerosis is the common pathological basis of coronary heart disease and many other cardiovascular diseases [3, 17]
Accumulating studies indicate that lncRNAs are involved in the process of injury and repair of endothelial cells, migration and proliferation of smooth muscle cells, lipid loading and inflammatory response in macrophages, and lipid deposition and the formation of plaques, all of which affect the progression of atherosclerosis and other cardiovascular diseases [4, 21, 23]
Top 10 upregulated and downregulated mRNAs in advanced atherosclerotic plaques compared with normal arterial intimae
Summary
Atherosclerosis is the common pathological basis of coronary heart disease and many other cardiovascular diseases [3, 17]. The pathogenesis of atherosclerosis is complex, involving lipid deposition, vascular smooth muscle cell proliferation and apoptosis, endothelial cell dysfunction, and macrophage foam cell formation [7, 9]. LncRNAs are involved in many biological processes such as chromatin modification, transcription, splicing, translation, degradation, and transport and have effects on growth, metabolism, and senescence through cell proliferation, differentiation, and apoptosis [8, 31, 33, 34, 41]. Accumulating studies indicate that lncRNAs are involved in the process of injury and repair of endothelial cells, migration and proliferation of smooth muscle cells, lipid loading and inflammatory response in macrophages, and lipid deposition and the formation of plaques, all of which affect the progression of atherosclerosis and other cardiovascular diseases [4, 21, 23].
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