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PMID: 9665460 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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.

The American journal of pathology ·Vol. 153 ·No. 1 ·1998-07-00 ·Pages 17-23

Marx N, Sukhova G, Murphy C, Libby P, Plutzky J

Abstract

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.

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,enzymology Prostaglandin D2/analogs & derivatives,pharmacology RNA, Messenger/analysis Receptors, Cytoplasmic and Nuclear/metabolism Tetradecanoylphorbol Acetate/pharmacology Thiazoles/pharmacology Thiazolidinediones Transcription Factors/metabolism Troglitazone
Chemicals
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
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Marx N
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Sukhova G
Murphy C
Libby P
Plutzky J
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/s0002-9440(10)65540-x
Published
1998-07-00
Pages
17-23
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1852950
Subset
IM
Grants
NHLBI NIH HHS · P50HL56985 · United States
NHLBI NIH HHS · R37HL34636 · United States
NHLBI NIH HHS · HL 03107 · United States
External Links
PubMed source DOI: 10.1016/s0002-9440(10)65540-x PMC Full Text View journal details
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