Matrix metalloproteinase-9 and spontaneous hemorrhage in an animal model of cerebral amyloid angiopathy.
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.
Lee
Jin-Moo
JM
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
Yin
Ke-Jie
KJ
Hsin
Idar
I
Chen
Shawei
S
Fryer
John D
JD
Holtzman
David M
DM
Hsu
Chung Y
CY
Xu
Jian
J
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
D016229:Amyloid beta-Peptides; D020780:Matrix Metalloproteinase 9