15-deoxy-δ 12,14 prostaglandin J 2 reduces the formation of atherosclerotic lesions in apolipoprotein e knockout mice

Abstract

Aim: 15-Deoxy-Δ 12,14 Prostaglandin J 2 (15d-PGJ 2) is a ligand of peroxisome proliferator-activated receptor γ (PPARγ) having diverse effects such as the differentiation of adipocytes and atherosclerotic lesion formation. 15d-PGJ 2 can also regulate the expression of inflammatory mediators on immune cells independent of PPARγ. We investigated the antiatherogenic effect of 15d-PGJ 2. Methods: We fed apolipoprotein (apo) E-deficient female mice a Western-type diet from 8 to 16 wk of age and administered 1 mg/kg/day 15d-PGJ 2 intraperitoneally. We measured atherosclerotic lesions at the aortic root, and examined the expression of macrophage and inflammatory atherosclerotic molecules by immunohistochemical and real-time PCR in the lesion. Results: Atherosclerotic lesion formation was reduced in apo E-null mice treated with 15d-PGJ 2, as compared to in the controls. Immunohistochemical and real-time PCR analyses showed that the expression of MCP-1, TNF-α, and MMP-9 in atherosclerotic lesions was significantly decreased in 15d-PGJ 2 treated mice. The 15d-PGJ 2 also reduced the expression of macrophages and RelA mRNA in atherosclerotic lesions. Conclusion: This is the first report 15d-PGJ 2, a natural PPARγ agonist, can improve atherosclerotic lesions in vivo. 15d-PGJ 2 may be a beneficial therapeutic agent for atherosclerosis. © 2011 Seno et al.