Macrophages in human atheroma contain PPARgamma: differentiation-dependent peroxisomal proliferator-activated receptor gamma(PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro

Am J Pathol. 1998 Jul;153(1):17-23. doi: 10.1016/s0002-9440(10)65540-x.


Mononuclear phagocytes play an important role in atherosclerosis and its sequela plaque rupture in part by their secretion of matrix metalloproteinases (MMPs), including MMP-9. Peroxisomal proliferator-activated receptor gamma (PPARgamma), a transcription factor in the nuclear receptor superfamily, regulates gene expression in response to various activators, including 15-deoxy-delta12,14-prostaglandin J2 and the antidiabetic agent troglitazone. The role of PPARgamma in human atherosclerosis is unexplored. We report here that monocytes/macrophages in human atherosclerotic lesions (n = 12) express immunostainable PPARgamma. Normal artery specimens (n = 6) reveal minimal immunoreactive PPARgamma. Human monocytes and monocyte-derived macrophages cultured for 6 days in 5% human serum expressed PPARgamma mRNA and protein by reverse transcription-polymerase chain reaction and Western blotting, respectively. In addition, PPARgamma mRNA expression in U937 cells increased during phorbol 12-myristate 13 acetate-induced differentiation. Stimulation of PPARgamma with troglitazone or 15-deoxy-delta12,14-prostaglandin J2 in human monocyte-derived macrophages inhibited MMP-9 gelatinolytic activity in a concentration-dependent fashion as revealed by zymography. This inhibition correlates with decreased MMP-9 secretion as determined by Western blotting. Thus, PPARgamma is present in macrophages in human atherosclerotic lesions and may regulate expression and activity of MMP-9, an enzyme implicated in plaque rupture. PPARgamma is likely to be an important regulator of monocyte/macrophage function with relevance for human atherosclerotic disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arteriosclerosis / enzymology*
  • Blotting, Northern
  • Blotting, Western
  • Cell Line
  • Cells, Cultured
  • Chromans / pharmacology
  • Collagenases / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Macrophages / enzymology*
  • Matrix Metalloproteinase 9
  • Monocytes / drug effects
  • Monocytes / enzymology*
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / pharmacology
  • RNA, Messenger / analysis
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / metabolism*
  • Troglitazone


  • Chromans
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • 9-deoxy-delta-9-prostaglandin D2
  • Collagenases
  • Matrix Metalloproteinase 9
  • Troglitazone
  • Tetradecanoylphorbol Acetate
  • Prostaglandin D2