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Matrix metalloproteinase-9 mediates post-hypoxic vascular pruning of cerebral blood vessels by degrading laminin and claudin-5

Academic Article
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Overview

authors

  • Boroujerdi, A.
  • Welser-Alves, J. V.
  • Milner, Richard

publication date

  • July 2015

journal

  • Angiogenesis  Journal

abstract

  • Vascular remodeling involves a highly coordinated break-down and build-up of the vascular basal lamina and inter-endothelial tight junction proteins. In light of the important role of matrix metalloproteinases (MMPs) in tissue remodeling, the goal of this study was to examine the role of MMP-9 in remodeling of cerebral blood vessels, both in hypoxia-induced angiogenesis and in the vascular pruning that accompanies the switch from hypoxia back to normoxia. In a chronic mild hypoxia model of cerebrovascular remodeling, gel zymography revealed that MMP-9 levels were increased, both during hypoxic-induced angiogenesis and in the post-hypoxic pruning response. Interestingly, compared to wild-type mice, MMP-9 KO mice showed no alteration in hypoxic-induced angiogenesis, but did show marked delay in post-hypoxic vascular pruning. In wild-type mice, vascular pruning was associated with fragmentation of vascular laminin and the tight junction protein claudin-5, while this process was markedly attenuated in MMP-9 KO mice. In vitro experiments showed that hypoxia stimulated MMP-9 expression in brain endothelial cells but not pericytes. These results show that while MMP-9 is not essential for hypoxic-induced cerebral angiogenesis, it plays an important role in post-hypoxic vascular pruning by degrading laminin and claudin-5.

subject areas

  • Animals
  • Anoxia
  • Antigens, CD31
  • Brain
  • Cells, Cultured
  • Cerebrovascular Circulation
  • Claudin-5
  • Endothelial Cells
  • Immunohistochemistry
  • Laminin
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pericytes
  • Time Factors
  • Up-Regulation
  • Vascular Remodeling
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Research

keywords

  • Claudin-5
  • Endothelial cell
  • Hypoxia
  • Laminin
  • Matrix metalloproteinase-9
  • Vascular remodeling
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Identity

International Standard Serial Number (ISSN)

  • 0969-6970

Digital Object Identifier (DOI)

  • 10.1007/s10456-015-9464-7

PubMed ID

  • 25812799
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Additional Document Info

start page

  • 255

end page

  • 264

volume

  • 18

issue

  • 3

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