RAMP2-AS1 Regulates Endothelial Homeostasis and Aging

The homeostasis of vascular endothelium is crucial for cardiovascular health and endothelial cell (EC) aging and dysfunction could negatively impact vascular function. Leveraging time-series transcriptomic data obtained from endothelial cells (ECs) subjected to physiological pulsatile flow versus pathophysiological oscillatory flow, we performed principal component analysis (PCA) to identify key genes contributing to divergent transcriptional states of ECs under distinct flow patterns. Through bioinformatics analysis, we identified that a long non-coding RNA (lncRNA) RAMP2- AS1 encoded on the antisense of RAMP2, a determinant of endothelial homeostasis and vascular integrity, is a novel regulator essential for EC homeostasis and function. Knockdown of RAMP2-AS1 inhibited EC angiogenesis and promoted EC senescence, as a result of extensive changes of EC transcriptome. Our study demonstrates an integrative approach to quantifying EC aging based on transcriptome changes, which also identified a number of novel regulators, including protein-coding genes and many lncRNAs involved EC functional modulation. Principal component analysis of time-series transcriptome data identified novel regulators, including protein-coding and non-coding genes, for EC biology and vascular aging. RAMP2-AS1 is a key long non-coding RNA regulating EC homeostasis.