Matrix metalloproteinase-9 and spontaneous hemorrhage in an animal model of cerebral amyloid angiopathy

Ann Neurol. 2003 Sep;54(3):379-82. doi: 10.1002/ana.10671.

Abstract

We examined the potential role of the extra-cellular matrix-degrading enzyme, matrix metalloproteinase-9 (MMP-9), in the pathogenesis of cerebral amyloid angiopathy (CAA)-induced spontaneous hemorrhage. The amyloid-beta peptide (Abeta) induced the synthesis, release and activation of MMP-9 in murine cerebral endothelial cells, resulting in increased extracellular matrix degradation. Furthermore, extensive MMP-9 immunoreactivity was observed in CAA-vessels with evidence of microhemorrhage in aged APPsw transgenic mice, but not detected in aged wild type or young APPsw mice. These results suggest that increased vascular MMP-9 expression, stimulated by Abeta, may play a role in the pathogenesis of spontaneous intracerebral hemorrhage in patients with CAA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Blotting, Western
  • Capillaries / enzymology
  • Cells, Cultured
  • Cerebral Amyloid Angiopathy / complications
  • Cerebral Amyloid Angiopathy / enzymology*
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / cytology
  • Cerebral Hemorrhage / etiology*
  • Cerebrovascular Circulation / physiology
  • Endothelium, Vascular / enzymology*
  • Extracellular Matrix / metabolism
  • Immunohistochemistry
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Mice, Transgenic
  • Models, Animal

Substances

  • Amyloid beta-Peptides
  • Matrix Metalloproteinase 9