title: Matrix metalloproteinase-9 and spontaneous hemorrhage in an animal model of cerebral amyloid angiopathy.
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.
authors.affiliation: Department of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8111, St. Louis, MO, USA. leejm@neuro.wustl.edu
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Lee
authors.forename: Ke-Jie
authors.initials: KJ
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: D000375:Aging; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002196:Capillaries / Q000201:enzymology; D002478:Cells, Cultured; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000201:enzymology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology; D002543:Cerebral Hemorrhage / Q000209:etiology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000201:enzymology*; D005109:Extracellular Matrix / Q000378:metabolism; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal
chemical_list: D016229:Amyloid beta-Peptides; D020780:Matrix Metalloproteinase 9