Introduction: Long non-coding RNAs (lncRNAs) play key roles in the development of atherosclerosis through the inflammatory pathway. This study aimed to investigate the role of lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) in atherosclerosis via its function in A disintegrin and metalloprotease 10 (ADAM10).
Methods: Initially, the expression of CDKN2B-AS1 and ADAM10 in atherosclerotic plaque tissues and THP-1 macrophage-derived foam cells was determined, after which the cholesterol efflux rate of macrophages was calculated. Interaction between CDKN2B-AS1 and ADAM10 was analyzed, after which, expression of CDKN2B-AS1 and ADAM10 were altered to explore their effects on inflammatory response and cholesterol efflux. The aforementioned findings were further intended to be validated by the atherosclerosis mouse model experiments.
Results: Atherosclerotic plaque tissue and THP-1 macrophage-derived foam cells exhibited downregulated CDKN2B-AS1 and upregulated ADAM10. Upon overexpressing CDKN2B-AS1 or silencing ADAM10, lipid accumulation was reduced and cholesterol efflux was increased. CDKN2B-AS1 located in the nucleus could bind to DNA methyltransferase 1 (DNMT1) to enhance methylation of ADAM10 promoter, leading to suppressed atherosclerotic inflammatory response and promoted cholesterol efflux.
Conclusion: Altogether, lncRNA CDKN2B-AS1 can inhibit the transcription of ADAM10 via DNMT1-mediated ADAM10 DNA methylation, consequently preventing inflammatory response of atherosclerosis and promoting cholesterol efflux.
Keywords: ADAM10; DNMT1; atherosclerosis; cholesterol efflux; inflammatory response; long non-coding RNA CDKN2B-AS1.