| RRC ID |
63628
|
| 著者 |
Matsuo M, Nadanaka S, Soga M, Sugiyama T, Serigano S, Shimano K, Ichinose F, Nakamura T, Maeda T, Houkin K, Era T, Kitagawa H.
|
| タイトル |
Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease.
|
| ジャーナル |
Sci Rep
|
| Abstract |
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.
|
| 巻・号 |
11(1)
|
| ページ |
1552
|
| 公開日 |
2021-1-15
|
| DOI |
10.1038/s41598-021-81282-9
|
| PII |
10.1038/s41598-021-81282-9
|
| PMID |
33452387
|
| PMC |
PMC7810726
|
| MeSH |
Adenosine Triphosphatases / metabolism
Adolescent
Aged
Biomechanical Phenomena / physiology
Carotid Artery, Internal / pathology
Carotid Intima-Media Thickness
Chondroitin Sulfates / analysis
Endothelial Cells / metabolism*
Endothelial Cells / physiology
Endothelium / metabolism
Female
Genetic Predisposition to Disease
Humans
Hyaluronic Acid / analysis
Hydrodynamics
Induced Pluripotent Stem Cells / metabolism
Male
Moyamoya Disease / metabolism
Moyamoya Disease / physiopathology*
Shear Strength / physiology
Stress, Mechanical
Ubiquitin-Protein Ligases / metabolism
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
409B2(HPS0076) |
