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Endothelial cell microparticles act as centers of matrix metalloproteinsase‐2 (MMP‐2) activation and vascular matrix remodeling

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Endothelial cell microparticles act as centers of matrix metalloproteinsase‐2 (MMP‐2) activation and vascular matrix remodeling

Auteurs : Thomas P. Lozito [États-Unis] ; Rocky S. Tuan [États-Unis]

Source :

Journal of Cellular Physiology [ 0021-9541 ] ; 2012-02.

RBID : ISTEX:CF56B77A871A61746F3030E019436D730DBABE37

English descriptors

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 αV. 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. J. Cell. Physiol. 227: 534–549, 2012. © 2011 Wiley Periodicals, Inc.

Url:

https://api.istex.fr/document/CF56B77A871A61746F3030E019436D730DBABE37/fulltext/pdf

DOI: 10.1002/jcp.22744

Affiliations:

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Le document en format XML

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<wicri:cityArea>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</wicri:cityArea>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Abcam</term>
<term>Activity assays</term>
<term>Apma</term>
<term>Apoptotic bodies</term>
<term>Assay</term>
<term>Avidin</term>
<term>Bind exogenous</term>
<term>Binding interactions</term>
<term>Biotin</term>
<term>Bronectin</term>
<term>Bronectin receptor</term>
<term>Bronectin receptors</term>
<term>Cellular</term>
<term>Cellular physiology</term>
<term>Combes</term>
<term>Control conditions</term>
<term>Culture conditions</term>
<term>Cytokine</term>
<term>Diamant</term>
<term>Edta</term>
<term>Elisa</term>
<term>Endogenous</term>
<term>Endothelial</term>
<term>Endothelial cells</term>
<term>Endothelial microparticles</term>
<term>Exogenous</term>
<term>Exogenous mmps</term>
<term>Extracellular</term>
<term>Extracellular matrix molecules</term>
<term>Gelatin</term>
<term>Gelatin zymography</term>
<term>High levels</term>
<term>Higher levels</term>
<term>Hypoxia</term>
<term>Hypoxic conditions</term>
<term>Inhibitor</term>
<term>Inhibitor assays</term>
<term>Integrin</term>
<term>Integrin avb3</term>
<term>Lozito</term>
<term>Matrix</term>
<term>Matrix metalloproteinases</term>
<term>Matrix molecules</term>
<term>Membrane</term>
<term>Membrane extracts</term>
<term>Metalloproteinases</term>
<term>Microec</term>
<term>Microec membrane extracts</term>
<term>Microecs</term>
<term>Microparticles</term>
<term>Mmmp</term>
<term>Mmmp results</term>
<term>Mmps</term>
<term>Monomeric avidin</term>
<term>Msc</term>
<term>Pathological conditions</term>
<term>Pellet</term>
<term>Perivascular</term>
<term>Perivascular niche</term>
<term>Photometry</term>
<term>Physiology</term>
<term>Protein samples</term>
<term>Receptor</term>
<term>Room temperature</term>
<term>Santa cruz</term>
<term>Substrate protein</term>
<term>Timps</term>
<term>Tuan</term>
<term>Ultracentrifugation pellets</term>
<term>Uorescence</term>
<term>Uorescence photometry</term>
<term>Uorescence scans</term>
<term>Uorescent</term>
<term>Vascular matrix</term>
<term>Vehicle control</term>
<term>Vehicle controls</term>
<term>Vesicle</term>
<term>Western blot</term>
<term>Western blot analysis</term>
<term>Western blots</term>
<term>Zymography</term>
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<keywords scheme="Teeft" xml:lang="en"><term>Abcam</term>
<term>Activity assays</term>
<term>Apma</term>
<term>Apoptotic bodies</term>
<term>Assay</term>
<term>Avidin</term>
<term>Bind exogenous</term>
<term>Binding interactions</term>
<term>Biotin</term>
<term>Bronectin</term>
<term>Bronectin receptor</term>
<term>Bronectin receptors</term>
<term>Cellular</term>
<term>Cellular physiology</term>
<term>Combes</term>
<term>Control conditions</term>
<term>Culture conditions</term>
<term>Cytokine</term>
<term>Diamant</term>
<term>Edta</term>
<term>Elisa</term>
<term>Endogenous</term>
<term>Endothelial</term>
<term>Endothelial cells</term>
<term>Endothelial microparticles</term>
<term>Exogenous</term>
<term>Exogenous mmps</term>
<term>Extracellular</term>
<term>Extracellular matrix molecules</term>
<term>Gelatin</term>
<term>Gelatin zymography</term>
<term>High levels</term>
<term>Higher levels</term>
<term>Hypoxia</term>
<term>Hypoxic conditions</term>
<term>Inhibitor</term>
<term>Inhibitor assays</term>
<term>Integrin</term>
<term>Integrin avb3</term>
<term>Lozito</term>
<term>Matrix</term>
<term>Matrix metalloproteinases</term>
<term>Matrix molecules</term>
<term>Membrane</term>
<term>Membrane extracts</term>
<term>Metalloproteinases</term>
<term>Microec</term>
<term>Microec membrane extracts</term>
<term>Microecs</term>
<term>Microparticles</term>
<term>Mmmp</term>
<term>Mmmp results</term>
<term>Mmps</term>
<term>Monomeric avidin</term>
<term>Msc</term>
<term>Pathological conditions</term>
<term>Pellet</term>
<term>Perivascular</term>
<term>Perivascular niche</term>
<term>Photometry</term>
<term>Physiology</term>
<term>Protein samples</term>
<term>Receptor</term>
<term>Room temperature</term>
<term>Santa cruz</term>
<term>Substrate protein</term>
<term>Timps</term>
<term>Tuan</term>
<term>Ultracentrifugation pellets</term>
<term>Uorescence</term>
<term>Uorescence photometry</term>
<term>Uorescence scans</term>
<term>Uorescent</term>
<term>Vascular matrix</term>
<term>Vehicle control</term>
<term>Vehicle controls</term>
<term>Vesicle</term>
<term>Western blot</term>
<term>Western blot analysis</term>
<term>Western blots</term>
<term>Zymography</term>
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<front><div type="abstract" xml:lang="en">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 αV. 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. J. Cell. Physiol. 227: 534–549, 2012. © 2011 Wiley Periodicals, Inc.</div>
</front>
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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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English descriptors

Abstract

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