Abstract 20197: A Role for Long Non-Coding RNAs in Atherosclerosis Development
Protein-coding genes account for only 2% of the human genome although greater than 90 % is actively transcribed. LncRNAs, arbitrarily defined as non-coding RNAs greater than 200 bp, represent the largest class of noncoding transcripts. LncRNAs are expressed in specific cellular contexts and may serve as signaling mediators integrating developmental cues. Our previous work identified the long noncoding RNA LeXis is an important regulator of systemic cholesterol metabolism and orchestrates crosstalk between the Liver X receptor (LXR) and sterol regulatory element-binding protein (SREBP) transcription factors. In this work, we show that another LXR regulated lncRNA mediates LXR-dependent macrophage cholesterol efflux in loss and gain function studies. In addition, using a bone marrow transplantation model we show that implantation of lncRNA null bone marrow in LDRL knockout mice markedly accelerates atherosclerosis development in comparison with WT bone marrow. These results establish lncRNAs as direct mediators of atherosclerosis development and uncovers novel regulatory pathways influencing sterol metabolism and atherogenesis.
Author Disclosures: T. Sallam: None. M. Jones: None. G. Thomas: None. X. Wu: None. P. Tontonoz: None.
- © 2016 by American Heart Association, Inc.