Steven Bensinger, VMD, PhD

University of California, Los Angeles, CA

2009 Cardiovascular System

Linking lupus, cardiovascular disease and lipid metabolism

Steven Bensinger, VMD, PhDIt'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.

Selected Publication:

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.