Oxidized low-density and high-density lipoproteins regulate the production of matrix metalloproteinase-1 and -9 by activated monocytes.
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)-alpha 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-alpha 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 E2 (PGE2)-dependent pathway as indomethacin suppressed and PGE2 restored MMP-1 production. This conclusion was supported further by ox-LDL-mediated increases in PGE2 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.
Ardans
Jeanette A
JA
Immunopathology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Economou
Antaeus P
AP
Martinson
James M
JM
Zhou
Min
M
Wahl
Larry M
LM
D002478:Cells, Cultured; D015232:Dinoprostone / Q000097:blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone