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

J Cell Physiol. 2012 Feb;227(2):534-49. doi: 10.1002/jcp.22744.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Line
  • Cell-Derived Microparticles / physiology*
  • Edetic Acid
  • Endothelial Cells / cytology*
  • Endothelial Cells / physiology*
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Gene Expression Regulation, Enzymologic / physiology*
  • Humans
  • Integrin alphaV / metabolism
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Protein Binding
  • Tissue Inhibitor of Metalloproteinases / metabolism

Substances

  • Fibronectins
  • Integrin alphaV
  • Tissue Inhibitor of Metalloproteinases
  • Edetic Acid
  • Matrix Metalloproteinase 2