The expression of matrix metalloproteinase-13 is increased in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model.
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.
Ueno
Masaki
M
Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan. masaueno@med.kagawa-u.ac.jp
Wu
Bin
B
Nishiyama
Akira
A
Huang
Cheng-long
CL
Hosomi
Naohisa
N
Kusaka
Takashi
T
Nakagawa
Toshitaka
T
Onodera
Masayuki
M
Kido
Mizue
M
Sakamoto
Haruhiko
H
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
D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9