2009 Cardiovascular System
Linking lupus, cardiovascular disease and lipid metabolism
It's still unclear why people with lupus have a more than 50-fold increased risk for cardiovascular problems such as accelerated atherosclerosis With LRI funding, Dr. Bensinger pursued the novel concept that a protein called the "Liver X Receptor" (LXR)-already a well-known player in promoting atherosclerosis and inflammation-may also contribute to the accelerated atherosclerosis of lupus. Dr. Bensinger had already reported that a deficiency of LXR in mice leads to the development of lupus-like disease, providing the first evidence that a single transcription factor may regulate the cause and development of both atherosclerosis and autoimmunity.
The results of Dr. Bensinger’s LRI-funded work showed that a protein (liver-X-receptor) best known for controlling cholesterol-levels is also essential to prevent lupus in mice. So defects in this protein could perhaps cause lupus and, at the same time, increase a patient’s risk of cardiovascular disease. Dr. Bensinger has recently discovered an unexpected role for liver-x-receptor proteins in preventing an excess accumulation of cells that cause inflammation in tissues. These findings, published in the Journal of Clinical Investigation, help to explain how liver x receptor keeps autoimmune disease at bay – insight that could inform the development of new lupus therapies.
Coordinate regulation of neutrophil homeostasis by liver X receptors in mice. Hong C, Kidani Y, A-Gonzalez N, Phung T, Ito A, Rong X, Ericson K, Mikkola H, Beaven SW, Miller LS, Shao WH, Cohen PL, Castrillo A, Tontonoz P, Bensinger SJ. J Clin Invest. 2012 Jan 3;122(1):337-47.