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.
Highlights
Moyamoya disease (MMD) is characterized by progressive bilateral stenotic changes in the terminal portion of the internal carotid arteries
Staining of samples for HA with HA-binding protein revealed marked accumulation of HA in the thickened intima of a specimen from a patient with MMD, whereas in the control specimens, HA staining was detected in the endothelium and in the outside margins of the internal elastic lamina, with only a small amount of HA detected within the intima
There was weak staining for cyclooxygenase 2 (COX2) in the infiltrated cells in the thickened intima and vascular smooth muscle cells (VSMCs) of the specimen from the patient with MMD, and comparable COX2 staining in the VSMCs in both control specimens (Fig. 1I–L)
Summary
Moyamoya disease (MMD) is characterized by progressive bilateral stenotic changes in the terminal portion of the internal carotid arteries. 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. Moyamoya disease (MMD) is characterized by progressive stenotic changes in the terminal portion of the bilateral internal carotid arteries (ICA)[1,2]. These stenotic changes result in the formation of fine collateral vessels (‘moyamoya’ vessels) at the base of the brain. A computational fluid dynamics model was developed to show the distribution of values for vascular WSS in the predisposing region of MMD
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
