Three papers in the January issue of Nature Medicine (Vol. 7, Issue 1, 01 Jan 2001) discuss the role of an exciting new receptor that is found in the nucleus of cells called peroxisome proliferator-activated receptors (PPARs) in cholesterol uptake and atherosclerosis.
PPARs are thought to be involved in diseases such as diabetes, obesity, atherosclerosis and cancer. Indeed, rostroglitazone and pioglitazone belong to a class of drugs (thiazolidinediones) that acts on PPAR receptors and has been developed for diabetes. Further understanding of PPAR function could lead to the development of new therapies for all these diseases.
Bart Staels and colleagues from the Pasteur Institute in France show that stimulation of PPAR-gamma and alpha receptors increases the expression of another molecule called ABCA1 that exports cholesterol from cells called macrophages. Exploiting this pathway may be a way to control lipid levels, inflammation and atherosclerosis in the body. Mason Freeman and colleagues at Harvard Medical School also report on the differing effects that stimulating these receptors has on cholesterol movement in and out of macrophages.
In a separate paper, Ronald Evans and colleagues of the Salk Institute for Biological Studies found that the PPAR-gamma receptor is not required for the development of macrophages, and that thiazolidinedione drugs inhibit cytokine production and inflammation in cells that lack PPAR-gamma, suggesting that these drugs target multiple pathways.
Mitch Lazar of the University of Pennsylvania School of Medicine discusses the implications of these findings for cardiovascular diseases in an accompanying News & Views article.
Dr. Bart Staels
Institut Pasteurde Lille
1 rue Calmete BP245
Tel: +33 3 20 87 73 60
Dr. Mason W. Freeman
Lipid Metabolism Unit, GRJ 1328
Massachusetts General Hospital
Harvard Medical School
55 Fruit Street
Boston, MA 02114
Tel: +1 617 726 5906
Dr. Ronald M. Evans
Howard Hughes Medical Institute
Gene Expression Laboratory
The Salk Institute for Biological Studies
10010 N. Torrey Pines Rd.
La Jolla, CA 92037
Tel: +1 858 453 4100, Ext.1302
Dr. Mitch Lazar
Division of Endocrinology, Diabetes, and Metabolism
University of Pennsylvania School of Medicine
415 Curie Blvd.
Philadelphia, PA 19104
Tel: +1 215 898 0210
(C) Nature Medicine press release.
Message posted by: Trevor M. D'Souza