Regulatory Roles of Related Long Non-coding RNAs in the Process of Atherosclerosis

Abstract

Atherosclerosis (AS) is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular disease, which comprise serious hazards to human health. Atherosclerosis is characterized by the deposition of lipids on the interior walls of blood vessels, causing an inflammatory response of immune cells, endothelial cells, and smooth muscle cells, and a proliferation cascade reaction. Despite years of research, the underlying pathogenesis of AS is not fully defined. Recent advances in our understanding of the molecular mechanisms by which non-coding RNA influences the initiation and progression of AS have shown that long non-coding RNAs (lncRNAs) regulate important stages in the atherosclerotic process. In this review, we summarize current knowledge of lncRNAs, which influence the development of AS. We review the regulatory processes of lncRNAs on core stages of atherosclerotic progression, including lipid metabolism, inflammation, vascular cell proliferation, apoptosis, adhesion and migration, and angiogenesis. A growing body of evidence suggests that lncRNAs have great potential as new therapeutic targets for the treatment of vascular diseases.

Keywords: angiogenesis; atherosclerosis; inflammatory response; lipid metabolism; lncRNA; vascular cells.

FIGURE 1

Schematic of long non-coding RNAs regulating atherosclerotic processes. The upper row depicts lncRNAs that promote the development of atherosclerosis, whereas, the lower row shows lncRNAs that inhibit the development of atherosclerosis. NFIA, nuclear factor I-A; APOA1, apolipoprotein A1; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; ox-LDL, oxidized low-density lipoprotein; MLKL, mixed lineage kinase domain-like protein; PTEN, phosphatase and tensin homolog deleted on chromosome 10; HAS2, hyaluronan synthase 2; ROR2, receptor tyrosine kinase-like orphan receptor 2; RhoA, ras homolog gene family member A; MCL-1, myeloid cell leukemia-1; VEGF, vascular endothelial growth factor; GPR119, G protein coupled receptor 119; ABCA1, ATP binding cassette transporter A1; KLF4, Kruppel-like factor 4; BRG1, brahma-related gene 1 protein; MDM2, mouse double minute 2; ICAM-1, intercellular cell adhesion molecule-1; MAPK6, mitogen-activated protein kinase 6.