Background : Long noncoding RNAs (lncRNA) provide a new layer of gene expression control and are crucial for vascular development and cardiovascular disease. We set out to identify novel endothelial lncRNAs which could be exploited to treat vascular disease.

Methods and Results: A search for differentially expressed and cell-specific lncRNAs in RNA-seq datasets identified “prostate cancer associated transcript 19”  (PCAT19) as a top candidate. PCAT19 is restricted to human endothelial cells and is induced by cellular confluence as observed in cultured endothelial cells. Knockdown of PCAT19 increased endothelial proliferation and migration, while overexpression had the opposite effect. Importantly, this also applied to angiogenic capacity, wherein depletion of PCAT19 increased endothelial spheroid outgrowth potential. RNA-seq after knockdown of the lncRNA suggested that PCAT19 affects genes associated with cell-cycle progression, particularly G1- to S-phase transition, as well as the p53 DNA damage response pathway and DNA replication and repair. PCAT19 pulldown experiments followed by mass spectrometry identified multiple DNA damage response proteins as interaction partners of PCAT19. Assays to investigate DNA double-strand breaks, including TUNEL and Comet assays, revealed that depletion of PCAT19 results in substantial levels of DNA damage.