Activation of peroxisome proliferator-activated receptor gamma inhibits osteoprotegerin gene expression in human aortic smooth muscle cells.
Increasing evidence indicates an important role of PPAR gamma activation in modulating the development and progression of atherosclerosis, however, the mechanisms involved in these effects are not well understood since the PPAR gamma-regulated genes in vascular smooth muscle cells (VSMC) are poorly defined. Here we reported that PPAR gamma 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 PPAR gamma antagonist. Overexpression of PPAR gamma in HASMC by the infection of a PPAR gamma adenovirus dramatically decreased OPG expression. In addition, PPAR gamma activation inhibited OPG promoter activity. Taken together, our data suggest that OPG expression is a novel PPAR gamma target gene in VSMC and downregulation of OPG expression by PPAR gamma activation provides a new insight into the understanding of the role of PPAR gamma in atheroscelrosis and hypertension.
Fu
Mingui
M
Cardiovascular Research Institute, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310, USA.
Zhang
Jifeng
J
Lin Yg
Yimin g
Yg
Zhu
Xiaojun
X
Willson
Timothy M
TM
Chen
Yuqing E
YE
D001161:Arteriosclerosis / Q000235:genetics / Q000503:physiopathology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology*
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D014157:Transcription Factors