Dysregulation of RNF213 promotes cerebral hypoperfusion

Abstract RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rn...

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Autores principales:	Takaaki Morimoto, Jun-ichiro Enmi, Yorito Hattori, Satoshi Iguchi, Satoshi Saito, Kouji H. Harada, Hiroko Okuda, Yohei Mineharu, Yasushi Takagi, Shohab Youssefian, Hidehiro Iida, Susumu Miyamoto, Masafumi Ihara, Hatasu Kobayashi, Akio Koizumi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b969cc437d5b4540ab0359356b4517d8
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spelling	oai:doaj.org-article:b969cc437d5b4540ab0359356b4517d82021-12-02T15:08:00ZDysregulation of RNF213 promotes cerebral hypoperfusion10.1038/s41598-018-22064-82045-2322https://doaj.org/article/b969cc437d5b4540ab0359356b4517d82018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-22064-8https://doaj.org/toc/2045-2322Abstract RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rnf213 knockout (KO) and vascular endothelial cell-specific Rnf213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%; p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%; p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role of RNF213 in the maintenance of CBF.Takaaki MorimotoJun-ichiro EnmiYorito HattoriSatoshi IguchiSatoshi SaitoKouji H. HaradaHiroko OkudaYohei MineharuYasushi TakagiShohab YoussefianHidehiro IidaSusumu MiyamotoMasafumi IharaHatasu KobayashiAkio KoizumiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takaaki Morimoto Jun-ichiro Enmi Yorito Hattori Satoshi Iguchi Satoshi Saito Kouji H. Harada Hiroko Okuda Yohei Mineharu Yasushi Takagi Shohab Youssefian Hidehiro Iida Susumu Miyamoto Masafumi Ihara Hatasu Kobayashi Akio Koizumi Dysregulation of RNF213 promotes cerebral hypoperfusion
description	Abstract RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rnf213 knockout (KO) and vascular endothelial cell-specific Rnf213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%; p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%; p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role of RNF213 in the maintenance of CBF.
format	article
author	Takaaki Morimoto Jun-ichiro Enmi Yorito Hattori Satoshi Iguchi Satoshi Saito Kouji H. Harada Hiroko Okuda Yohei Mineharu Yasushi Takagi Shohab Youssefian Hidehiro Iida Susumu Miyamoto Masafumi Ihara Hatasu Kobayashi Akio Koizumi
author_facet	Takaaki Morimoto Jun-ichiro Enmi Yorito Hattori Satoshi Iguchi Satoshi Saito Kouji H. Harada Hiroko Okuda Yohei Mineharu Yasushi Takagi Shohab Youssefian Hidehiro Iida Susumu Miyamoto Masafumi Ihara Hatasu Kobayashi Akio Koizumi
author_sort	Takaaki Morimoto
title	Dysregulation of RNF213 promotes cerebral hypoperfusion
title_short	Dysregulation of RNF213 promotes cerebral hypoperfusion
title_full	Dysregulation of RNF213 promotes cerebral hypoperfusion
title_fullStr	Dysregulation of RNF213 promotes cerebral hypoperfusion
title_full_unstemmed	Dysregulation of RNF213 promotes cerebral hypoperfusion
title_sort	dysregulation of rnf213 promotes cerebral hypoperfusion
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/b969cc437d5b4540ab0359356b4517d8
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Dysregulation of RNF213 promotes cerebral hypoperfusion

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