Long-Non-Coding RNA HypERrlnc Regulates Human Pericyte Function by Modulation of the Endoplasmic Reticulum-Stress Cell Response

Introduction: Pericytes are perivascular mural cells that induce vessel maturation and endothelial barrier function. Long non-coding RNAs (lncRNAs) are known to influence endothelial cell function, but their role in pericyte biology remains unexplored. Endoplasmic reticulum (ER) stress is a common cellular response upon stimuli such as hypoxia that triggers cell death and consecutive organ dysfunction. Here we show that lncRNA HypeERlnc (Hypoxia-Induced Endoplasmic Reticulum-Stress Regulating RNA) affects pericyte function by modulating the ER-stress cell response. Methods and Results: RNA seq identified 30 hypoxia regulated lncRNAs in primary human pericytes (hPC), including HypERrlnc. Silencing HypERrlnc, which is enriched in the nucleus (nucleus/cytosol ratio: 1.55±0.09, n=3), with LNA-GapmeRs decreased cell viability (MTT assay: 0.77±0.02 vs Ctrl, P Conclusion: LncRNA HypERrlnc regulates the evolution of ER-stress and is important for pericyte survival, proliferation, differentiation, coronary endothelial recruitment and endothelial barrier function. Moreover, downregulation of HypERrlnc in chronic heart failure indicates a role of HypERrlnc in human cardiac disease.