Increased MMP activity in curved geometries disrupts the endothelial cell glycocalyx creating a proinflammatory environment

PLoS One. 2018 Aug 23;13(8):e0202526. doi: 10.1371/journal.pone.0202526. eCollection 2018.

Abstract

Wall shear stress gradients (WSSGs) induce an inflammatory phenotype in endothelial cells (ECs) which is hypothesized to be mediated by mechanotransduction through the EC glycocalyx (GCX). We used a three-dimensional in vitro cell culture model with a 180o curved geometry to investigate if WSSGs created by curvature can cause EC inflammation and disruption of the GCX. The hydrodynamics of the model elicited a morphological response in ECs as well as a pattern of leukocyte adhesion towards the inner wall of curvature that was attenuated with enzymatic removal of GCX components. GCX degradation was also observed in regions of curvature which corresponded to increased activity of MMPs. Together, these results support the hypothesis that the EC GCX is involved in mechanotransduction of WSSGs and that components of the GCX are regulated by MMP activity in regions of curvature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aorta, Abdominal / cytology
  • Cell Culture Techniques / methods*
  • Endothelial Cells / chemistry
  • Endothelial Cells / cytology
  • Glycocalyx / chemistry
  • Glycocalyx / metabolism
  • Humans
  • Hydrodynamics
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Matrix Metalloproteinases / chemistry
  • Matrix Metalloproteinases / genetics*
  • Mechanotransduction, Cellular / genetics*
  • Stress, Mechanical

Substances

  • Matrix Metalloproteinases

Grants and funding

This work was funded by grant 261938-13 from the Natural Sciences and Engineering Research Council of Canada to RL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.