Oxidized low-density lipoproteins stimulate extracellular matrix metalloproteinase Inducer (EMMPRIN) release by coronary smooth muscle cells.
OBJECTIVE
Matrix metalloproteinases (MMPs) seem to play a prominent role in atherogenesis. Extracellular MMP inducer (EMMPRIN), a cell surface glycoprotein which stimulates MMP synthesis, has recently been detected in human atheroma. We have investigated the influence of oxidized low-density lipoproteins (oxLDLs) on EMMPRIN expression in human coronary artery smooth muscle cells (HCA-SMCs).


RESULTS
OxLDL induced a significant increase of EMMPRIN release into HCA-SMC supernatants and a concomitant decrease of cell-associated EMMPRIN. These effects were antagonized by antioxidants as well as by EDTA and the MMP inhibitor GM6001. Western blot analysis demonstrated that MMP-1 and MMP-2 induce the cleavage of the extracellular domain from cell-associated EMMPRIN. MMP-1 and MMP-2 synthesis was upregulated by oxLDL, and, in addition, we have shown that soluble EMMPRIN, isolated from macrophage supernatants, increased MMP-1 and MMP-2 synthesis in HCA-SMC.


CONCLUSIONS
Our data suggest that oxLDLs stimulate the release of soluble EMMPRIN, at least in part, by MMP-dependent shedding from the cell surface. Additionally, oxLDLs might induce a circular upregulation of matrix degradation because, in turn, soluble EMMPRIN stimulates MMP synthesis in HCA-SMC.
Haug
Cornelia
C
Central Department Clinical Chemistry, University Hospital Ulm, Robert-Koch-Strasse 8, D-89070 Ulm, Germany. cornelia.haug@medizin.uni-ulm.de.
Lenz
Christina
C
Díaz
Fredy
F
Bachem
Max G
MG
D015703:Antigens, CD; D051926:Basigin; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000737:chemistry; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D015703:Antigens, CD; C497886:BSG protein, human; D008077:Lipoproteins, LDL; D011994:Recombinant Proteins; C099252:oxidized low density lipoprotein; D051926:Basigin; D020782:Matrix Metalloproteinases