title: The expression of matrix metalloproteinase-13 is increased in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model.
abstract: We previously reported that the blood-brain barrier (BBB) function was deteriorated in vessels located in the hippocampus, but not the cerebral cortex, in 3-month-old stroke-prone spontaneously hypertensive rats (SHRSP). Recently published data suggest that matrix metalloproteinase (MMP)-2 and MMP-9 play a critical role in the BBB disruption in stroke or cerebral ischemia. In this study, we examined gene and protein expressions of MMPs in the BBB-damaged hippocampal vessels of 3-month-old SHRSP, in the cerebral cortical vessels without BBB damage of SHRSP, and in the hippocampal and cerebral cortical ones without BBB damage of 3-month-old Wistar Kyoto (WKY) rats. The expressions of MMPs were examined by real-time quantitative reverse transcriptase-PCR (RT-PCR), western blotting and immunohistochemical techniques. The gene and protein expressions of MMP-13 were significantly increased in the hippocampal samples of SHRSP compared with samples without BBB damage, such as cerebral cortical samples of SHRSP or hippocampal samples of WKY. Immunostaining of MMP-13 was seen in the cytoplasm of ED-1-positive perivascular cells in both rats and was colocalized with those of type IV collagen or osteopontin. The type IV collagen was also localized in the basement membrane. These findings indicate that the expression of MMP-13 is increased in BBB-damaged hippocampal vessels in hypertensive SHRSP compared with vessels without BBB impairment in normotensive WKY rats and may be involved in vascular remodeling.
authors.affiliation: Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan. masaueno@med.kagawa-u.ac.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Cheng-long
authors.initials: CL
authors.lastname: Huang
authors.forename: Naohisa
authors.initials: N
authors.lastname: Hosomi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kusaka
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Onodera
authors.forename: Mizue
authors.initials: M
authors.lastname: Kido
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sakamoto
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology* / Q000473:pathology; D002536:Cerebral Arteries / Q000201:enzymology* / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000201:enzymology; D006624:Hippocampus / Q000098:blood supply / Q000201:enzymology; D006973:Hypertension / Q000150:complications / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis* / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000201:enzymology* / Q000209:etiology / Q000473:pathology
chemical_list: D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9