title: Endothelial cell microparticles act as centers of matrix metalloproteinsase-2 (MMP-2) activation and vascular matrix remodeling.
abstract: Endothelial cell (EC)-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 α(V) . MPs isolated from EC-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 but 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.
authors: Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
authors: Thomas P
authors: TP
authors: Lozito
authors: Rocky S
authors: RS
authors: Tuan
mesh_terms: D000818:Animals; D002460:Cell Line; D055252:Cell-Derived Microparticles / Q000502:physiology*; D004492:Edetic Acid; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
chemical_list: D005353:Fibronectins; D039564:Integrin alphaV; D019714:Tissue Inhibitor of Metalloproteinases; D004492:Edetic Acid; D020778:Matrix Metalloproteinase 2