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Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke

Recent clinical studies suggest that pentraxin 3 (PTX3), which is known as an acute‐phase protein that is produced rapidly at local sites of inflammation, may be a new biomarker of disease risk for central nervous system disorders, including stroke. However, the effects of PTX3 on cerebrovascular fu...

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Autores principales: Shindo, Akihiro, Takase, Hajime, Hamanaka, Gen, Chung, Kelly K., Mandeville, Emiri T., Egawa, Naohiro, Maki, Takakuni, Borlongan, Mia, Takahashi, Ryosuke, Lok, Josephine, Tomimoto, Hidekazu, Lo, Eng H., Arai, Ken
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804900/
https://www.ncbi.nlm.nih.gov/pubmed/33314664
http://dx.doi.org/10.1111/cns.13510
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author Shindo, Akihiro
Takase, Hajime
Hamanaka, Gen
Chung, Kelly K.
Mandeville, Emiri T.
Egawa, Naohiro
Maki, Takakuni
Borlongan, Mia
Takahashi, Ryosuke
Lok, Josephine
Tomimoto, Hidekazu
Lo, Eng H.
Arai, Ken
author_facet Shindo, Akihiro
Takase, Hajime
Hamanaka, Gen
Chung, Kelly K.
Mandeville, Emiri T.
Egawa, Naohiro
Maki, Takakuni
Borlongan, Mia
Takahashi, Ryosuke
Lok, Josephine
Tomimoto, Hidekazu
Lo, Eng H.
Arai, Ken
author_sort Shindo, Akihiro
collection PubMed
description Recent clinical studies suggest that pentraxin 3 (PTX3), which is known as an acute‐phase protein that is produced rapidly at local sites of inflammation, may be a new biomarker of disease risk for central nervous system disorders, including stroke. However, the effects of PTX3 on cerebrovascular function in the neurovascular unit (NVU) after stroke are mostly unknown, and the basic research regarding the roles of PTX3 in NVU function is still limited. In this reverse translational study, we prepared mouse models of white matter stroke by vasoconstrictor (ET‐1 or L‐Nio) injection into the corpus callosum region to examine the roles of PTX3 in the pathology of cerebral white matter stroke. PTX3 expression was upregulated in GFAP‐positive astrocytes around the affected region in white matter for at least 21 days after vasoconstrictor injection. When PTX3 expression was reduced by PTX3 siRNA, blood‐brain barrier (BBB) damage at day 3 after white matter stroke was exacerbated. In contrast, when PTX3 siRNA was administered at day 7 after white matter stroke, compensatory angiogenesis at day 21 was promoted. In vitro cell culture experiments confirmed the inhibitory effect of PTX3 in angiogenesis, that is, recombinant PTX3 suppressed the tube formation of cultured endothelial cells in a Matrigel‐based in vitro angiogenesis assay. Taken together, our findings may support a novel concept that astrocyte‐derived PTX3 plays biphasic roles in cerebrovascular function after white matter stroke; additionally, it may also provide a proof‐of‐concept that PTX3 could be a therapeutic target for white matter‐related diseases, including stroke.
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spelling pubmed-78049002021-01-29 Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke Shindo, Akihiro Takase, Hajime Hamanaka, Gen Chung, Kelly K. Mandeville, Emiri T. Egawa, Naohiro Maki, Takakuni Borlongan, Mia Takahashi, Ryosuke Lok, Josephine Tomimoto, Hidekazu Lo, Eng H. Arai, Ken CNS Neurosci Ther Original Articles Recent clinical studies suggest that pentraxin 3 (PTX3), which is known as an acute‐phase protein that is produced rapidly at local sites of inflammation, may be a new biomarker of disease risk for central nervous system disorders, including stroke. However, the effects of PTX3 on cerebrovascular function in the neurovascular unit (NVU) after stroke are mostly unknown, and the basic research regarding the roles of PTX3 in NVU function is still limited. In this reverse translational study, we prepared mouse models of white matter stroke by vasoconstrictor (ET‐1 or L‐Nio) injection into the corpus callosum region to examine the roles of PTX3 in the pathology of cerebral white matter stroke. PTX3 expression was upregulated in GFAP‐positive astrocytes around the affected region in white matter for at least 21 days after vasoconstrictor injection. When PTX3 expression was reduced by PTX3 siRNA, blood‐brain barrier (BBB) damage at day 3 after white matter stroke was exacerbated. In contrast, when PTX3 siRNA was administered at day 7 after white matter stroke, compensatory angiogenesis at day 21 was promoted. In vitro cell culture experiments confirmed the inhibitory effect of PTX3 in angiogenesis, that is, recombinant PTX3 suppressed the tube formation of cultured endothelial cells in a Matrigel‐based in vitro angiogenesis assay. Taken together, our findings may support a novel concept that astrocyte‐derived PTX3 plays biphasic roles in cerebrovascular function after white matter stroke; additionally, it may also provide a proof‐of‐concept that PTX3 could be a therapeutic target for white matter‐related diseases, including stroke. John Wiley and Sons Inc. 2020-12-11 /pmc/articles/PMC7804900/ /pubmed/33314664 http://dx.doi.org/10.1111/cns.13510 Text en © 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Shindo, Akihiro
Takase, Hajime
Hamanaka, Gen
Chung, Kelly K.
Mandeville, Emiri T.
Egawa, Naohiro
Maki, Takakuni
Borlongan, Mia
Takahashi, Ryosuke
Lok, Josephine
Tomimoto, Hidekazu
Lo, Eng H.
Arai, Ken
Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke
title Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke
title_full Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke
title_fullStr Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke
title_full_unstemmed Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke
title_short Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke
title_sort biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804900/
https://www.ncbi.nlm.nih.gov/pubmed/33314664
http://dx.doi.org/10.1111/cns.13510
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