In the December 1 issue of the Journal of Clinical Investigation, Andrew Li and colleagues from the University of California, San Diego compare the effects of PPARalpha, PPARbeta, and PPARgamma agonists on the development of atherosclerosis in a mouse model of this disease. They observed profound protective effects of the PPARalpha agonist GW7647, comparable to the PPARgamma agonist rosiglitazone that is currently used to treat type 2 diabetes. GW7647 also reduced weight gain, and insulin and lipoprotein levels. In contrast, lesion development was not inhibited by a PPARbeta agonist.
In an accompanying commentary, Peter Tontonoz and Antonio Castrillo from the University of California, Los Angeles discuss the mechanism described by Li and colleagues by which lipid accumulation is reduced by these agonists, thereby giving us a greater understanding of the roles of PPAR family members in atherosclerosis. Most importantly, the study highlights that the use of a drug (or drugs) that target multiple PPARs, particularly PPARalpha and PPARgamma, may be effective in limiting the accumulation of lipid in macrophages and subsequently reversing atherosclerosis.
TITLE: Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARalpha, beta/delta, and gamma
AUTHOR CONTACT:
Andrew C. Li or Christopher K. Glass
Department of Cellular and Molecular Medicine
University of California, San Diego, USA
Phone: 858-534-0575 or 858-524-0611
Fax: 858-822-2127 or 858-822-2127
E-mail: acli@ucsd.edu or cglass@ucsd.edu .
View the PDF of this article at: http://www.jci.org/cgi/content/full/114/11/1564
ACCOMPANYING COMMENTARY:
TITLE: PPARs in atherosclerosis: the clot thickens
AUTHOR CONTACT:
Peter Tontonoz
Howard Hughes Medical Institute
UCLA, Los Angeles, California, USA
Phone: 310-206-4546
Fax: 310-267-0382,br> E-mail: ptontonoz@mednet.ucla.edu .
Journal of Clinical Investigation