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The endothelium is crucially involved in the pathogenesis of atherosclerosis according to accumulating evidence. Moreover, recent studies have showed that lncRNAs could serve as biomarkers of cardiovascular diseases, in particular atherosclerosis. However, the underlying mechanism of endothelial dysfunction involving lncRNAs in atherosclerosis remains unknown. This study investigated the mechanism of lncRNA XXYLT1-AS2 in endothelial dysfunction in atherosclerosis. The levels of lncRNA XXYLT1-AS2 , FUS, VCAM-1, MCP-1, p-AKT, and p-P65 were measured in arteries and HUVEC cell lines via quantitative real-time PCR or Western blot. FISH assay demonstrated that XXYLT1-AS2 and FUS are localized in the nucleus. HUVECs were transfected with si- XXYLT1-AS2 or XXYLT1-AS2 to further assess cell proliferation, migration, and adhesion. Furthermore, bioinformatics analysis, RNA immunoprecipitation and immunofluorescence were performed to investigate the target genes of XXYLT1-AS2 and possible signal pathways. Overexpression of XXYLT1-AS2 inhibited cell proliferation and migration, reduced the expression of adhesion molecules (VCAM-1) and chemoattractant proteins (MCP-1), and restrained monocyte adhesion to endothelial cells. Mechanistic investigations indicated that XXYLT1-AS2 directly interacts with the target gene FUS/cyclin D1 and modulates the proliferation and migration of endothelial cells (ECs). Moreover, XXYLT1-AS2 exerts a protective role against the inflammatory response in atherosclerosis by blocking NF-κB activity. Clinically, the involvement of XXYLT1-AS2 /FUS was also observed in human arteries and the results were consistent with the in vitro analysis. Our study identified a novel long non-coding RNA (XXYLT1-AS2) and suggests that it might act as an underlying therapeutic target in atherosclerosis-related diseases by regulating ECs functions. Image 1 • LncRNA XXYLT1-AS2 modulates endothelial dysfunction to serve as a critical repressor of atherosclerosis. • LncRNA XXYLT1-AS2 upregulated FUS expression, thereby inhibiting HUVEC proliferation and migration via repressing cyclin D1. • LncRNA XXYLT1-AS2 negatively regulated monocyte adhesion and the level of VCAM-1 and MCP-1 by targeting NF-κB pathway. [ABSTRACT FROM AUTHOR]

Angiogenesis is the physiological process of new blood vessel formation from existing capillary vessels or posterior capillary veins. Its dysfunction could result in a number of diseases, such as cardiovascular diseases and cancer, contributing to death and disability worldwide. Circular RNAs (circRNAs) are a class of novel identified RNA molecules with a special covalent loop structure without a 5′ cap and 3' tail, which can lead to novel back-splicing or skipping events from precursor mRNAs. Accumulating evidence suggests that circRNA play critical roles in diseases; in particular, they are abundantly and abnormally expressed in angiogenesis-related diseases. In this review, we describe the role of circRNA under pathological conditions, discuss the association between circRNA and angiogenesis, classify the regulatory mechanisms and suggest that circRNA can be used as potential therapeutic targets for angiogenesis-related diseases under clinical evaluation. Image 1 • circRNAs are critically involved in angiogenesis, angiocardiopathy and cancer. • circRNAs are stable and abundantly distributed indicating a potential role in diseases. • circRNA might target miRNA as a sponge and are an emerging therapeutic target for angiogenesis-related diseases. • The research of coding potential of circRNA suggests the possible effective treatment of related diseases in the future. [ABSTRACT FROM AUTHOR]