Pioglitozone inhibits the progression, but does not reverse development of atherosclerosis, in LDL receptor‐deficient mice

• Published in: The FASEB journal 2006-03, Vol.20 (5), p.A1075-A1075
• Main Authors: Nakaya, Hideaki, Nicholson, Andrew C, Han, Jihong, Summers, Barbara, Gotto, Antonio M, Hajjar, David P
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.5.A1075-b

Peroxisome proliferator‐activated receptor‐γ (PPARγ) is a ligand‐activated transcriptional regulator of genes encoding proteins involved in adipogenesis, lipid metabolism and glucose homeostasis. Synthetic ligands of PPARγ (thiazolidinediones such as pioglitazone) are utilized for improving insulin resistance. PPARγ ligands have been shown to inhibit the development of atherosclerosis in murine models of this disease, but their effect on preexisting atherosclerosis is unknown. We tested the hypothesis that pioglitazone could reverse atherosclerosis in LDL‐receptor null (LDLR−/−) mice. Methods LDLR−/− mice (5 week old males) were divided into 3 groups (20 mice/group) and fed a high fat diet for 8 weeks. At this time 1/3 of the mice were sacrificed to establish a baseline of atherosclerotic lesion development. The remaining mice were continued on a high fat diet and half were given pioglitazone (15mg/kg/day) in the diet for 6 more weeks prior to sacrifice. Aortas were dissected and neutral lipid was stained with oil‐red‐o. Lipid stained lesion areas were quantified. rtPCR was performed using peritoneal macrophage RNA to quantify mRNA of efflux proteins, ABCA1/G1. Results Lesion area in pioglitazone‐treated mice was 36% less (p