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Activation of peroxisome proliferator-activated receptor inhibits osteoprotegerin gene expression in human aortic smooth muscle cells

2002; Elsevier BV; Volume: 294; Issue: 3 Linguagem: Inglês

10.1016/s0006-291x(02)00533-8

1090-2104

Mingui Fu, Jifeng Zhang, Yimin g Lin, Xiaojun Zhu, Timothy M. Willson, Yuqing E. Chen,

Lipoproteins and Cardiovascular Health

Increasing evidence indicates an important role of PPARγ activation in modulating the development and progression of atherosclerosis, however, the mechanisms involved in these effects are not well understood since the PPARγ-regulated genes in vascular smooth muscle cells (VSMC) are poorly defined. Here we reported that PPARγ ligands, GW7845, ciglitazone and troglitazone had the effect of inhibiting osteoprotegerin (OPG) expression in human aortic smooth muscle cells (HASMC). The effect of GW7845 and ciglitazone on OPG expression was completely abolished by GW9662, a PPARγ antagonist. Overexpression of PPARγ in HASMC by the infection of a PPARγ adenovirus dramatically decreased OPG expression. In addition, PPARγ activation inhibited OPG promoter activity. Taken together, our data suggest that OPG expression is a novel PPARγ target gene in VSMC and downregulation of OPG expression by PPARγ activation provides a new insight into the understanding of the role of PPARγ in atheroscelrosis and hypertension.