Matrix metalloproteinase-9 in cerebral-amyloid-angiopathy-related hemorrhage

Jin Moo Lee, Kejie Yin, Idar Hsin, Shawei Chen, John D. Fryer, David M. Holtzman, Chung Y. Hsu, Jian Xu

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Spontaneous intracerebral hemorrhage (ICH) is one of the most recognized complications of cerebral amyloid angiopathy (CAA), but little is known about the molecular pathogenesis of this life-threatening complication. In this review, we present preliminary evidence which suggests that the extracellular-matrix-degrading protease, matrix metalloproteinase-9 (MMP-9), may play a role in the development of spontaneous ICH resulting from CAA. The amyloid-beta peptide (Aβ) induced the synthesis, cellular release, and activation of MMP-9 in murine cerebral endothelial cells (CECs), resulting in increased extracellular matrix (ECM) degradation. Furthermore, in a mouse model of CAA (APPsw transgenic mice), MMP-9 immunoreactivity was observed in amyloid-laden cerebral vessels in aged APPsw mice but not in young APPsw or aged wild-type mice. More extensive MMP-9 immunostaining was present in amyloid-laden vessels with evidence of microhemorrhage. These results suggest that increased vascular MMP-9 expression, stimulated by Aβ, may play a role in the pathogenesis of spontaneous intracerebral hemorrhage (ICH) in patients with CAA.

Original languageEnglish
Pages (from-to)249-254
Number of pages6
JournalJournal of the Neurological Sciences
Volume229-230
DOIs
Publication statusPublished - Mar 15 2005

Keywords

  • Alzheimer's disease
  • Amyloid-beta peptide
  • Cerebral amyloid angiopathy
  • Endothelial cells
  • Intracerebral hemorrhage
  • Matrix metalloproteinase-9, gelatinase B

ASJC Scopus subject areas

  • Ageing
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

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  • Cite this

    Lee, J. M., Yin, K., Hsin, I., Chen, S., Fryer, J. D., Holtzman, D. M., Hsu, C. Y., & Xu, J. (2005). Matrix metalloproteinase-9 in cerebral-amyloid-angiopathy-related hemorrhage. Journal of the Neurological Sciences, 229-230, 249-254. https://doi.org/10.1016/j.jns.2004.11.041