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Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease

Moyamoya disease (MMD) is characterized by progressive bilateral stenotic changes in the terminal portion of the internal carotid arteries. Although RNF213 was identified as a susceptibility gene for MMD, the exact pathogenesis remains unknown. Immunohistochemical analysis of autopsy specimens from...

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Autores principales: Matsuo, Muneaki, Nadanaka, Satomi, Soga, Minami, Sugiyama, Taku, Serigano, Shota, Shimano, Kenjiro, Ichinose, Fumio, Nakamura, Takuji, Maeda, Toshiyuki, Houkin, Kiyohiro, Era, Takumi, Kitagawa, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810726/
https://www.ncbi.nlm.nih.gov/pubmed/33452387
http://dx.doi.org/10.1038/s41598-021-81282-9
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author Matsuo, Muneaki
Nadanaka, Satomi
Soga, Minami
Sugiyama, Taku
Serigano, Shota
Shimano, Kenjiro
Ichinose, Fumio
Nakamura, Takuji
Maeda, Toshiyuki
Houkin, Kiyohiro
Era, Takumi
Kitagawa, Hiroshi
author_facet Matsuo, Muneaki
Nadanaka, Satomi
Soga, Minami
Sugiyama, Taku
Serigano, Shota
Shimano, Kenjiro
Ichinose, Fumio
Nakamura, Takuji
Maeda, Toshiyuki
Houkin, Kiyohiro
Era, Takumi
Kitagawa, Hiroshi
author_sort Matsuo, Muneaki
collection PubMed
description Moyamoya disease (MMD) is characterized by progressive bilateral stenotic changes in the terminal portion of the internal carotid arteries. Although RNF213 was identified as a susceptibility gene for MMD, the exact pathogenesis remains unknown. Immunohistochemical analysis of autopsy specimens from a patient with MMD revealed marked accumulation of hyaluronan and chondroitin sulfate (CS) in the thickened intima of occlusive lesions of MMD. Hyaluronan synthase 2 was strongly expressed in endothelial progenitor cells in the thickened intima. Furthermore, MMD lesions showed minimal staining for CS and hyaluronan in the endothelium, in contrast to control endothelium showing positive staining for both. Glycosaminoglycans of endothelial cells derived from MMD and control induced pluripotent stem cells demonstrated a decreased amount of CS, especially sulfated CS, in MMD. A computational fluid dynamics model showed highest wall shear stress values in the terminal portion of the internal carotid artery, which is the predisposing region in MMD. Because the peri-endothelial extracellular matrix plays an important role in protection, cell adhesion and migration, an altered peri-endothelial matrix in MMD may contribute to endothelial vulnerability to wall shear stress. Invading endothelial progenitor cells repairing endothelial injury would produce excessive hyaluronan and CS in the intima, and cause vascular stenosis.
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spelling pubmed-78107262021-01-21 Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease Matsuo, Muneaki Nadanaka, Satomi Soga, Minami Sugiyama, Taku Serigano, Shota Shimano, Kenjiro Ichinose, Fumio Nakamura, Takuji Maeda, Toshiyuki Houkin, Kiyohiro Era, Takumi Kitagawa, Hiroshi Sci Rep Article Moyamoya disease (MMD) is characterized by progressive bilateral stenotic changes in the terminal portion of the internal carotid arteries. Although RNF213 was identified as a susceptibility gene for MMD, the exact pathogenesis remains unknown. Immunohistochemical analysis of autopsy specimens from a patient with MMD revealed marked accumulation of hyaluronan and chondroitin sulfate (CS) in the thickened intima of occlusive lesions of MMD. Hyaluronan synthase 2 was strongly expressed in endothelial progenitor cells in the thickened intima. Furthermore, MMD lesions showed minimal staining for CS and hyaluronan in the endothelium, in contrast to control endothelium showing positive staining for both. Glycosaminoglycans of endothelial cells derived from MMD and control induced pluripotent stem cells demonstrated a decreased amount of CS, especially sulfated CS, in MMD. A computational fluid dynamics model showed highest wall shear stress values in the terminal portion of the internal carotid artery, which is the predisposing region in MMD. Because the peri-endothelial extracellular matrix plays an important role in protection, cell adhesion and migration, an altered peri-endothelial matrix in MMD may contribute to endothelial vulnerability to wall shear stress. Invading endothelial progenitor cells repairing endothelial injury would produce excessive hyaluronan and CS in the intima, and cause vascular stenosis. Nature Publishing Group UK 2021-01-15 /pmc/articles/PMC7810726/ /pubmed/33452387 http://dx.doi.org/10.1038/s41598-021-81282-9 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Matsuo, Muneaki
Nadanaka, Satomi
Soga, Minami
Sugiyama, Taku
Serigano, Shota
Shimano, Kenjiro
Ichinose, Fumio
Nakamura, Takuji
Maeda, Toshiyuki
Houkin, Kiyohiro
Era, Takumi
Kitagawa, Hiroshi
Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease
title Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease
title_full Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease
title_fullStr Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease
title_full_unstemmed Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease
title_short Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease
title_sort vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of moyamoya disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810726/
https://www.ncbi.nlm.nih.gov/pubmed/33452387
http://dx.doi.org/10.1038/s41598-021-81282-9
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