Abstract
Pericytes are mural cells abundantly present in cerebral microvessels and play important roles, including the formation and maintenance of the blood-brain barrier. Nox4 is a major source of reactive oxygen species in cardiovascular cells and modulate cellular functions, particularly under pathological conditions. In the present study, we found that the expression of Nox4 was markedly induced in microvascular cells, including pericytes, in peri-infarct areas after middle cerebral artery occlusion stroke models in mice. The upregulation of Nox4 was greater in a permanent middle cerebral artery occlusion model compared with an ischemia/reperfusion transient middle cerebral artery occlusion model. We performed permanent middle cerebral artery occlusion on mice with Nox4 overexpression in pericytes (Tg-Nox4). Infarct volume was significantly greater with enhanced reactive oxygen species production and blood-brain barrier breakdown in peri-infarct areas in Tg-Nox4, compared with littermate controls. In cultured brain pericytes, Nox4 was significantly upregulated by hypoxia and was promptly downregulated by reoxygenation. Phosphorylation of NFκ B and production of matrix metalloproteinase 9 were significantly increased in both cultured pericytes overexpressing Nox4 and in peri-infarct areas in Tg-Nox4. Collectively, Nox4 is upregulated in pericytes in peri-infarct areas after acute brain ischemia and may enhance blood-brain barrier breakdown through activation of NFκ B and matrix metalloproteinase 9, thereby causing enlargement of infarct volume.
| Original language | English |
|---|---|
| Pages (from-to) | 1143-1154 |
| Number of pages | 12 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 36 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2016 |
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All Science Journal Classification (ASJC) codes
- Neurology
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
Cite this
Detrimental role of pericyte Nox4 in the acute phase of brain ischemia. / Nishimura, Ataru; Ago, Tetsuro; Kuroda, Junya; Arimura, Koichi; Tachibana, Masaki; Nakamura, Kuniyuki; Wakisaka, Yoshinobu; Sadoshima, Junichi; Iihara, Koji; Kitazono, Takanari.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 36, No. 6, 01.06.2016, p. 1143-1154.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Detrimental role of pericyte Nox4 in the acute phase of brain ischemia
AU - Nishimura, Ataru
AU - Ago, Tetsuro
AU - Kuroda, Junya
AU - Arimura, Koichi
AU - Tachibana, Masaki
AU - Nakamura, Kuniyuki
AU - Wakisaka, Yoshinobu
AU - Sadoshima, Junichi
AU - Iihara, Koji
AU - Kitazono, Takanari
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Pericytes are mural cells abundantly present in cerebral microvessels and play important roles, including the formation and maintenance of the blood-brain barrier. Nox4 is a major source of reactive oxygen species in cardiovascular cells and modulate cellular functions, particularly under pathological conditions. In the present study, we found that the expression of Nox4 was markedly induced in microvascular cells, including pericytes, in peri-infarct areas after middle cerebral artery occlusion stroke models in mice. The upregulation of Nox4 was greater in a permanent middle cerebral artery occlusion model compared with an ischemia/reperfusion transient middle cerebral artery occlusion model. We performed permanent middle cerebral artery occlusion on mice with Nox4 overexpression in pericytes (Tg-Nox4). Infarct volume was significantly greater with enhanced reactive oxygen species production and blood-brain barrier breakdown in peri-infarct areas in Tg-Nox4, compared with littermate controls. In cultured brain pericytes, Nox4 was significantly upregulated by hypoxia and was promptly downregulated by reoxygenation. Phosphorylation of NFκ B and production of matrix metalloproteinase 9 were significantly increased in both cultured pericytes overexpressing Nox4 and in peri-infarct areas in Tg-Nox4. Collectively, Nox4 is upregulated in pericytes in peri-infarct areas after acute brain ischemia and may enhance blood-brain barrier breakdown through activation of NFκ B and matrix metalloproteinase 9, thereby causing enlargement of infarct volume.
AB - Pericytes are mural cells abundantly present in cerebral microvessels and play important roles, including the formation and maintenance of the blood-brain barrier. Nox4 is a major source of reactive oxygen species in cardiovascular cells and modulate cellular functions, particularly under pathological conditions. In the present study, we found that the expression of Nox4 was markedly induced in microvascular cells, including pericytes, in peri-infarct areas after middle cerebral artery occlusion stroke models in mice. The upregulation of Nox4 was greater in a permanent middle cerebral artery occlusion model compared with an ischemia/reperfusion transient middle cerebral artery occlusion model. We performed permanent middle cerebral artery occlusion on mice with Nox4 overexpression in pericytes (Tg-Nox4). Infarct volume was significantly greater with enhanced reactive oxygen species production and blood-brain barrier breakdown in peri-infarct areas in Tg-Nox4, compared with littermate controls. In cultured brain pericytes, Nox4 was significantly upregulated by hypoxia and was promptly downregulated by reoxygenation. Phosphorylation of NFκ B and production of matrix metalloproteinase 9 were significantly increased in both cultured pericytes overexpressing Nox4 and in peri-infarct areas in Tg-Nox4. Collectively, Nox4 is upregulated in pericytes in peri-infarct areas after acute brain ischemia and may enhance blood-brain barrier breakdown through activation of NFκ B and matrix metalloproteinase 9, thereby causing enlargement of infarct volume.
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U2 - 10.1177/0271678X15606456
DO - 10.1177/0271678X15606456
M3 - Article
C2 - 26661159
AN - SCOPUS:84973322290
VL - 36
SP - 1143
EP - 1154
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 6
ER -