Endothelial cell microparticles act as centers of matrix metalloproteinsase-2 (MMP-2) activation and vascular matrix remodeling.
Endothelial cell microparticles act as centers of matrix metalloproteinsase-2 (MMP-2) activation and vascular matrix remodeling.
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DOI：
10.1002/jcp.22744
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发表时间：
2012-02
影响因子：
5.6
通讯作者：
Tuan, Rocky S.
中科院分区：
文献类型：
--
作者：
Lozito, Thomas P.;Tuan, Rocky S.
内皮细胞衍生的微粒子(MPS)是一种与多种血管病变相关的膜小泡。在这里，我们通过分析MPS与细胞外基质的相互作用来研究MPS在基质重塑中的作用。MPS通过整合素αV与纤维连接蛋白结合，而从内皮细胞条件培养液中分离的MPS显著富含包括基质金属蛋白酶(MMPs)在内的基质改变蛋白。MPS缺乏Sup中发现的基质金属蛋白酶抑制物TIMP-1和TIMP-2，而Sup强烈抑制MPS的活性，而MPS则没有。事实上，MPS可以结合和激活内源性和外源性的基质金属蛋白酶原-2。综上所述，这些结果表明，MPS与细胞外基质相互作用，在那里它们定位并激活基质金属蛋白酶-2来修饰周围的基质分子。这些发现提供了对血管基质重塑的细胞机制的见解，并确定了血管病理学的新靶点。
Endothelial cell derived microparticles (MPs) are small membrane vesicles associated with various vascular pathologies. Here we investigated the role of MPs in matrix remodeling by analyzing their interactions with the extracellular matrix. MPs were shown to bind preferentially to surfaces coated with matrix molecules, and MPs bound fibronectin via integrin αV. MPs isolated from endothelial cell-conditioned medium (Sup) were significantly enriched for matrix-altering proteases, including matrix metalloproteinases (MMPs). MPs lacked the MMP-inhibitors TIMP-1 and TIMP-2 found in the Sup and, while Sup strongly inhibited MMP activities, MPs did not. In fact, MPs were shown to bind and activate both endogenous and exogenous proMMP-2. Taken together, these results indicate that MPs interact with extracellular matrices, where they localize and activate MMP-2 to modify the surrounding matrix molecules. These findings provide insights into the cellular mechanisms of vascular matrix remodeling and identify new targets of vascular pathologies.
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