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Oxidized low‐density and high‐density lipoproteins regulate the production of matrix metalloproteinase‐1 and ‐9 by activated monocytes
Author(s) -
Ardans Jeanette A.,
Economou Antaeus P.,
Martinson James M.,
Zhou Min,
Wahl Larry M.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.71.6.1012
Subject(s) - matrix metalloproteinase , biology , microbiology and biotechnology , matrix (chemical analysis) , monocyte , metalloproteinase , matrix metalloproteinase 9 , biochemistry , biophysics , immunology , chemistry , chromatography
Monocytes/macrophages are prominent in atherosclerotic plaques where the vascular remodeling and plaque rupture may be influenced by the lipids and cytokines at these sites. Therefore, we evaluated the effects of factors found within the vascular wall, such as cytokines, oxidized low‐density lipoprotein (ox‐LDL), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL), on monocyte‐derived matrix metalloproteinase‐1 (MMP‐1) and ‐9 (MMP‐9) and tissue inhibitor of metalloproteinases‐1 (TIMP‐1). ox‐LDL, LDL, and HDL alone had no effect on MMP‐1, MMP‐9, or TIMP‐1 production. However, in the presence of tumor necrosis factor (TNF)‐α and GM‐CSF, ox‐LDL enhanced MMP‐1 significantly by two‐ to threefold, increased MMP‐9 slightly, and had no effect on TIMP‐1 production. In contrast, HDL suppressed the induction of MMP‐1 by TNF‐α and GM‐CSF as well as the ox‐LDL‐mediated increase in MMP‐1 production. The enhancement of MMP‐1 production by ox‐LDL occurred through, in part, a prostaglandin E 2 (PGE 2 )‐dependent pathway as indomethacin suppressed and PGE 2 restored MMP‐1 production. This conclusion was supported further by ox‐LDL‐mediated increases in PGE 2 and cyclooxygenase‐2 (COX‐2) production. These data suggest that the interaction of primary monocytes with ox‐LDL and proinflammatory cytokines may contribute to vascular remodeling and plaque rupture.