title: Matrix metalloproteinase-9 in cerebral-amyloid-angiopathy-related hemorrhage.
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 (Abeta) 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 Abeta, may play a role in the pathogenesis of spontaneous intracerebral hemorrhage (ICH) in patients with CAA.
authors.affiliation: Department of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, MO 63110, USA. leejm@neuro.wustl.edu
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Lee
authors.forename: Kejie
authors.initials: K
authors.lastname: Yin
authors.forename: Idar
authors.initials: I
authors.lastname: Hsin
authors.forename: Shawei
authors.initials: S
authors.lastname: Chen
authors.forename: John D
authors.initials: JD
authors.lastname: Fryer
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.forename: Chung Y
authors.initials: CY
authors.lastname: Hsu
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology; D005109:Extracellular Matrix / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D020780:Matrix Metalloproteinase 9