Vascular Smooth Muscle Cell Derived from IPS Cell of Moyamoya Disease - Comparative Characterization with Endothelial Cell Transcriptome

Tokairin, Kikutaro; Hamauchi, Shuji; Ito, Masaki; Kazumata, Ken; Sugiyama, Taku; Nakayama, Naoki; Kawabori, Masahito; Osanai, Toshiya; Houkin, Kiyohiro

doi:10.1016/j.jstrokecerebrovasdis.2020.105305

Cited by 19 publications

(15 citation statements)

References 28 publications

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“…Effect of the p.R4810K in VSMCs were reported by Tokairin et al By using VSMCs from iPS-derived neural crest stem cells, they showed that there was no significant difference in VSMC markers, cellular proliferation, migration, or contractile abilities between patients with the p.R4810K mutation and controls ( 62 ). Gene expression patterns of iPS-derived VSMCs were similar between patients and controls, whereas iPS-derived ECs displayed distinct patterns.…”

Section: Functions Of Rnf213 and Sgc In The Vascular Wall And Circulationmentioning

confidence: 87%

RNF213 and GUCY1A3 in Moyamoya Disease: Key Regulators of Metabolism, Inflammation, and Vascular Stability

Mineharu

Miyamoto

2021

Front. Neurol.

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Moyamoya disease is an idiopathic chronically progressive cerebrovascular disease, which causes both ischemic and hemorrhagic stroke. Genetic studies identified RNF213/Mysterin and GUCY1A3 as disease-causing genes. They were also known to be associated with non-moyamoya intracranial large artery disease, coronary artery disease and pulmonary artery hypertension. This review focused on these two molecules and their strong linker, calcineurin/NFAT signaling and caveolin to understand the pathophysiology of moyamoya disease and related vascular diseases. They are important regulators of lipid metabolism especially lipotoxicity, NF-κB mediated inflammation, and nitric oxide-mediated vascular protection. Although intimal thickening with fibrosis and damaged vascular smooth muscle cells are the distinguishing features of moyamoya disease, origin of the fibrous tissue and the mechanism of smooth muscle cell damages remains not fully elucidated. Endothelial cells and smooth muscle cells have long been a focus of interest, but other vascular components such as immune cells and extracellular matrix also need to be investigated in future studies. Molecular research on moyamoya disease would give us a clue to understand the mechanism preserving vascular stability.

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Section: Functions Of Rnf213 and Sgc In The Vascular Wall And Circulationmentioning

confidence: 87%

RNF213 and GUCY1A3 in Moyamoya Disease: Key Regulators of Metabolism, Inflammation, and Vascular Stability

Mineharu

Miyamoto

2021

Front. Neurol.

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“…These cells displayed specific DEGs compared with the control group. Recently, Tokairin et al (81) characterized the VSMCs in MMD first in terms of the biological function and transcriptome profile. Both MMD and the control group displayed similar features of VSMCs, while ECs displayed distinct transcriptome profiles; the same EC features had also been validated previously (82).…”

Section: Cellular Modelmentioning

confidence: 99%

“…Overexpression of related factors in SMCs can help increase EPC adhesion and differentiation, migration, and proliferation (85,86). However, according to the data in MMD research, the pathological changes are driven mainly by ECs, and VSMCs and specific environmental factors may play an important role (81). In 2017, C-C motif chemokine ligand 5 (CCL5) secreted by ECFCs was found to significantly augment the migration activities of SMCs toward ECFCs (87).…”

Section: Cellular Modelmentioning

confidence: 99%

Experimental Animal Models for Moyamoya Disease: A Species-Oriented Scoping Review

et al. 2022

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Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of large intracranial arteries and a hazy network of basal collaterals called moyamoya vessels. The etiology and pathogenesis of MMD are still obscure. The biggest obstacles in the basic research of MMD are difficulty in obtaining specimens and the lack of an animal model. It is necessary to use appropriate and rationally designed animal models for the correct evaluation. Several animal models and methods have been developed to produce an effective MMD model, such as zebrafish, mice and rats, rabbits, primates, felines, canines, and peripheral blood cells, each with advantages and disadvantages. There are three mechanisms for developing animal models, including genetic, immunological/inflammatory, and ischemic animal models. This review aims to analyze the characteristics of currently available models, providing an overview of the animal models framework and the convenience of selecting model types for MMD research. It will be a great benefit to identify strategies for future model generations.

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“…Morimoto et al published results of bilateral common carotid artery stenosis surgery in RNF213-/-mice and vascular endothelial cell-specific RNF213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice, revealing a significantly stronger reduction of CBF in the RNF213-/-mice than in wild-type mice [156]. Induced pluripotent stem cells (iPSCs) have been generated by several research groups [157][158][159][160][161][162][163]. Angiogenic activities of iPSC-derived vascular endothelial cells (iPSECs) from carriers and patients were lower than those of wild-type donors [157].…”

Section: Experimental Researchmentioning

confidence: 99%

The Genetic Basis of Moyamoya Disease

Mertens

Graupera

Gerhardt

et al. 2021

Transl. Stroke Res.

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Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive spontaneous bilateral occlusion of the intracranial internal cerebral arteries (ICA) and their major branches with compensatory capillary collaterals resembling a “puff of smoke” (Japanese: Moyamoya) on cerebral angiography. These pathological alterations of the vessels are called Moyamoya arteriopathy or vasculopathy and a further distinction is made between primary and secondary MMD. Clinical presentation depends on age and population, with hemorrhage and ischemic infarcts in particular leading to severe neurological dysfunction or even death. Although the diagnostic suspicion can be posed by MRA or CTA, cerebral angiography is mandatory for diagnostic confirmation. Since no therapy to limit the stenotic lesions or the development of a collateral network is available, the only treatment established so far is surgical revascularization. The pathophysiology still remains unknown. Due to the early age of onset, familial cases and the variable incidence rate between different ethnic groups, the focus was put on genetic aspects early on. Several genetic risk loci as well as individual risk genes have been reported; however, few of them could be replicated in independent series. Linkage studies revealed linkage to the 17q25 locus. Multiple studies on the association of SNPs and MMD have been conducted, mainly focussing on the endothelium, smooth muscle cells, cytokines and growth factors. A variant of the RNF213 gene was shown to be strongly associated with MMD with a founder effect in the East Asian population. Although it is unknown how mutations in the RNF213 gene, encoding for a ubiquitously expressed 591 kDa cytosolic protein, lead to clinical features of MMD, RNF213 has been confirmed as a susceptibility gene in several studies with a gene dosage-dependent clinical phenotype, allowing preventive screening and possibly the development of new therapeutic approaches. This review focuses on the genetic basis of primary MMD only.

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Vascular Smooth Muscle Cell Derived from IPS Cell of Moyamoya Disease - Comparative Characterization with Endothelial Cell Transcriptome

Cited by 19 publications

References 28 publications

RNF213 and GUCY1A3 in Moyamoya Disease: Key Regulators of Metabolism, Inflammation, and Vascular Stability

RNF213 and GUCY1A3 in Moyamoya Disease: Key Regulators of Metabolism, Inflammation, and Vascular Stability

Experimental Animal Models for Moyamoya Disease: A Species-Oriented Scoping Review

The Genetic Basis of Moyamoya Disease

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