UCLA scientists have identified a gene called MeXis that may play a protective role in preventing heart disease. Their findings suggests that this gene acts within macrophages inside clogged arteries to help remove excess cholesterol from blood vessels by controlling cholesterol pump protein expression. Research is published in the journal Nature Medicine.
MeXis is an example of a “selfish” gene, one that is presumed to have no function because it does not make a protein product. However, recent studies have suggested that these so-called “unhelpful” genes can actually perform important biological functions without making proteins and instead producing a special class of molecules called long non-coding RNAs, or lncRNAs.
“What this study tells us is that lncRNAs are important for the inner workings of cells involved in the development of heart disease,” said Dr. Peter Tontonoz, senior author of the study. “Considering many genes like MeXis have completely unknown functions, our study suggests that further exploring how other long non-coding RNAs act will lead to exciting insights into both normal physiology and disease.”
In the study, researchers found that mice lacking MeXis had almost twice as many blockages in their blood vessels compared to mice with normal MeXis levels. In addition, boosting MeXis levels made cells more effective at removing excess cholesterol. In the next phase of the study, researchers will further explore how MeXis affects the function of cells in the artery wall and will test various approaches to altering MeXis activity. The researchers are interested in finding out if MeXis could be targeted for therapy of cardiovascular disease.
Citation: Sallam, Tamer, Marius Jones, Brandon J. Thomas, Xiaohui Wu, Thomas Gilliland, Kevin Qian, Ascia Eskin, David Casero, Zhengyi Zhang, Jaspreet Sandhu, David Salisbury, Prashant Rajbhandari, Mete Civelek, Cynthia Hong, Ayaka Ito, Xin Liu, Bence Daniel, Aldons J. Lusis, Julian Whitelegge, Laszlo Nagy, Antonio Castrillo, Stephen Smale, and Peter Tontonoz. “Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA.” Nature Medicine, 2018. doi:10.1038/nm.4479.
Funding: NIH/National Heart, Lung and Blood Institute, Burroughs Wellcome Fund Career Awards for Medical Scientists, UCLA Cardiovascular Discovery Fund, Lauren B. Leichtman and Arthur E. Levine Investigator Award.
Adapted from press release by the University of California Los Angles Health Sciences.