RNF213 Loss-of-Function Promotes Angiogenesis of Cerebral Microvascular Endothelial Cells in a Cellular State Dependent Manner

Roy, Vincent; Brodeur, Alyssa; Deschênes, Lydia Touzel; Dupré, Nicolas; Gros‐Louis, François

doi:10.3390/cells12010078

Cited by 10 publications

(2 citation statements)

References 58 publications

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“…[6][7][8] RNF213 plays diverse roles in angiogenic processes, including proliferation, migration, and capillary formation. 23 As a means of imaging the vessel wall, VWE represents contrast agent accumulation in the vessel wall, and the mechanism may be functional disruption of the vascular endothelial barrier, leading to leakage of the contrast agent into the vessel wall 24 . The mechanism of VWE in MMD has not been clearly defined.…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic risk factors and long-term outcomes of MRI vessel wall enhancement in moyamoya disease

Hao

Han

et al. 2023

Preprint

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Background: Intracranial vessel wall enhancement (VWE) on high-resolution magnetic resonance imaging (HRMRI) is associated with the progression and poor prognosis of moyamoya disease (MMD). However, the genetic background and risk factors for VWE in MMD have not been investigated. Therefore, this study assessed potential risk factors for VWE in MMD.<break><break>Methods: We evaluated MMD patients using HRMRI and traditional angiography examinations. The participants were divided into VWE group and non-VWE group based on the presence or absence of VWE on HRMRI. Logistic regression was performed to compare the risk factors for VWE in MMD. The incidence of cerebrovascular events of the different subgroups according to risk factors were compared using KaplanMeier survival and Cox regression.. STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines were followed for reporting our cohort study.<break><break>Results: We included 283 MMD patients, 84 of whom had VWE on HRMRI. The VWE group had higher modified Rankin Scale scores at admission (P = 0.014) and a higher incidence of ischemia and hemorrhage (P =0.002) than did the non-VWE group. Multiple logistics regression shows risk factors for VWE included the ring finger protein 213 (RNF213) pR4810K variant (OR: 2.01 [95% confidence interval (CI), 1.08 - 3.76]; P = 0.028), hyperhomocysteinemia (HHcy; OR: 5.08 [95% CI, 2.34 - 11.05], P < 0.001), and smoking history (OR, 3.49 [95% CI, 1.08-11.31], P = 0.037). During the follow-up of 63.9 13.2 months (medium 65 months), 18 recurrent stroke events occurred. Cox regression showed that VWE and RNF213 pR4810K variant were risk factors for follow-up stroke. <break><break>Conclusion: The RNF213 p.R4810K variant is strongly associated with VWE and poor prognosis in MMD. HHcy and smoking are independent risk factors for VWE; both are likely to induce the VWE phenomenon by affecting vascular endothelial function or causing vascular endothelial damage.

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Section: Discussionmentioning

confidence: 99%

Clinical and genetic risk factors and long-term outcomes of MRI vessel wall enhancement in moyamoya disease

Hao

Han

et al. 2023

Preprint

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“…74136, QIAGEN) as described by the manufacturer protocol. Gene expression was assessed using the One‐Color Microarray‐Based Gene Expression Analysis kit (Agilent Technologies) as previously described (Roy et al., 2022).…”

Section: Methodsmentioning

confidence: 99%

Heterozygous NF1 dermal fibroblasts modulate exosomal content to promote angiogenesis in a tissue‐engineered skin model of neurofibromatosis type‐1

Roy,

Paquet,

Touzel‐Deschênes

et al. 2023

Journal of Neurochemistry

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Neovascularization is a critical process in tumor progression and malignant transformation associated with neurofibromatosis type 1 (NF1). Indeed, fibroblasts are known to play a key role in the tumoral microenvironment modification by producing an abundant collagenous matrix, but their contribution in paracrine communication pathways is poorly understood. Here, we hypothesized that NF1 heterozygosis in human dermal fibroblasts could promote angiogenesis through exosomes secretion. The purposes of this study are to identify the NF1 fibroblast‐derived exosome protein contents and to determine their proangiogenic activity. Angiogenic proteome measurement confirmed the overexpression of VEGF and other proteins involved in vascularization. Tube formation of microvascular endothelial cells was also enhanced in presence of exosomes derived from NF1 skin fibroblasts. NF1 tissue‐engineered skin (NF1‐TES) generation showed a significantly denser microvessels networks compared to healthy controls. The reduction of exosomes production with an inhibitor treatment demonstrated a drastic decrease in blood vessel formation within the dermis. Our results suggest that NF1 haploinsufficiency alters the dermal fibroblast function and creates a pro‐angiogenic signal via exosomes, which increases the capillary formation. This study highlights the potential of targeting exosome secretion and angiogenesis for therapeutic interventions in NF1.image

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High-resolution MRI vessel wall enhancement in moyamoya disease: risk factors and clinical outcomes

Hao,

Han,

et al. 2024

Eur Radiol

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RNF213 Loss-of-Function Promotes Angiogenesis of Cerebral Microvascular Endothelial Cells in a Cellular State Dependent Manner

Cited by 10 publications

References 58 publications

Clinical and genetic risk factors and long-term outcomes of MRI vessel wall enhancement in moyamoya disease

Clinical and genetic risk factors and long-term outcomes of MRI vessel wall enhancement in moyamoya disease

Heterozygous NF1 dermal fibroblasts modulate exosomal content to promote angiogenesis in a tissue‐engineered skin model of neurofibromatosis type‐1

High-resolution MRI vessel wall enhancement in moyamoya disease: risk factors and clinical outcomes

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