Oxidized Low-Density Lipoproteins Stimulate Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Release by Coronary Smooth Muscle Cells
- 1 October 2004
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 24 (10), 1823-1829
- https://doi.org/10.1161/01.atv.0000142806.59283.11
Abstract
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).Methods and 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.Conclusion—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.Keywords
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