Oxidized low-density lipoproteins stimulate extracellular matrix metalloproteinase inducer (EMMPRIN) release by coronary smooth muscle cells
Oxidized low-density lipoproteins stimulate extracellular matrix metalloproteinase inducer (EMMPRIN) release by coronary smooth muscle cells
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DOI：
10.1161/01.atv.0000142806.59283.11
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发表时间：
2004-10-01
影响因子：
8.7
通讯作者：
Bachem, MG
中科院分区：
文献类型：
--
作者：
Haug, C;Lenz, C;Bachem, MG
目的-基质金属蛋白酶（MMPs）似乎在动脉粥样硬化中起着重要作用。细胞外MMP诱导剂（EMMPRIN）是一种刺激MMP合成的细胞表面糖蛋白，最近在人动脉粥样硬化中被检测到。我们研究了氧化低密度脂蛋白（oxldl）对人冠状动脉平滑肌细胞（HCA-SMCs） EMMPRIN表达的影响。方法和结果- OxLDL诱导EMMPRIN在HCA-SMC上清液中的释放显著增加，并伴随细胞相关EMMPRIN的降低。这些作用可被抗氧化剂、EDTA和MMP抑制剂GM6001所拮抗。Western blot分析表明，MMP-1和MMP-2诱导细胞相关EMMPRIN的胞外结构域的分裂。oxLDL上调了MMP-1和MMP-2的合成，此外，我们已经证明从巨噬细胞上清中分离的可溶性EMMPRIN增加了HCA-SMC中MMP-1和MMP-2的合成。结论-我们的数据表明，oxldl刺激可溶性EMMPRIN的释放，至少在一定程度上是通过mmp依赖性脱落从细胞表面释放的。此外，氧化低密度脂蛋白可能诱导基质降解的循环上调，因为可溶性EMMPRIN反过来刺激HCA-SMC中MMP的合成。
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.