Coronary artery disease (CAD) is a major atherosclerotic
cardiovascular disease and the leading cause of mortality globally. Long non-coding RNAs (lncRNAs) play crucial roles in CAD development. To date, the effect of
lncRNA non-coding RNA activated by DNA damage (NORAD) on
atherosclerosis in CAD remains unclear. The primary aim of this study was to investigate the effect of
lncRNA NORAD on vascular endothelial cell injury and
atherosclerosis. Here,
ox-LDL-treated human umbilical vein endothelial cells (HUVECs) and high-fat-diet (HFD)-fed
ApoE-/- mice were utilized as in vitro and in vivo models. The present study found that
lncRNA NORAD expression was increased in
ox-LDL-treated HUVECs and thoracic aorta of atherosclerotic mice, and knockdown of
lncRNA NORAD alleviated vascular endothelial cell injury and
atherosclerosis development in vitro and in vivo. Knockdown of
lncRNA NORAD aggravated
ox-LDL-reduced or
atherosclerosis-decreased
vascular endothelial growth factor (
VEGF) expression in HUVECs and thoracic aorta of mice to ameliorate vascular endothelial cell injury and
atherosclerosis development. Moreover, nucleus
lncRNA NORAD suppressed
VEGF gene transcription through enhancing H3K9 deacetylation via recruiting HDAC6 to the
VEGF gene promoter in
ox-LDL-treated HUVECs. In addition,
VEGF reduced FUS (
FUS RNA binding protein) expression by a negative feedback regulation in HUVECs. In summary,
lncRNA NORAD enhanced vascular endothelial cell injury and
atherosclerosis through suppressing
VEGF gene transcription via enhancing H3K9 deacetylation by recruiting HDAC6. The findings could facilitate discovering novel diagnostic markers and therapeutic targets for CAD.