Long noncoding RNA regulates endothelial cell activities associated with coronary artery disease by up-regulating , , and genes.

Coronary artery disease (CAD) is the leading cause of death worldwide. Long noncoding RNAs (lncRNAs) are a class of noncoding transcripts of > 200 nucleotides and are increasingly recognized as playing functional roles in physiology and disease. is an lncRNA gene mapped to the chromosome 9p21 genetic locus for CAD identified by the first series of genome-wide association studies (GWAS). However, 's role in CAD and the underlying molecular mechanism are unknown. Here, we show that the major transcript in endothelial cells (ECs) is with a much higher expression level in ECs than in THP-1 monocytes. Of note, expression was down-regulated in CAD coronary arteries compared with non-CAD arteries. DQ485454 overexpression significantly reduced monocyte adhesion to ECs, transendothelial monocyte migration (TEM), and EC migration, which are critical cellular processes involved in CAD initiation, whereas siRNA-mediated knockdown (KD) had the opposite effect. Microarray and follow-up quantitative RT-PCR analyses revealed that the KD down-regulated expression of , , , , , , , and genes and up-regulated and genes. Mechanistic studies disclosed that overexpression of , , and reversed the effects of KD on monocyte adhesion to ECs, TEM, and EC migration. These findings indicate that regulates EC functions directly related to CAD, supporting the hypothesis that is involved in CAD pathogenesis at the 9p21 genetic locus and identifying a molecular mechanism underlying lncRNA-mediated regulation of EC function and CAD development.