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Identifying the origin and mechanisms of pathological angiogenesis in neuroinflammatory diseases

ABSTRACT: Identifying the origin and mechanisms of pathological angiogenesis in neuroinflammatory diseases

PROVIDER: PRJNA867406 | ENA |

REPOSITORIES: ENA

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Identifying the origin and mechanisms of pathological angiogenesis in neuroinflammatory diseases

Project description:Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). Studies in human MS and its animal model experimental autoimmune encephalomyelitis (EAE) have shown that new abnormal vessels develop in demyelinating plaques through pathological neo-angiogenesis, which exacerbates MS/EAE pathology by contributing to the leakage of serum components and infiltration of immune cells into the CNS. However, the cellular origin and the signaling pathways underlying this pathology remain poorly understood. Here, using single-cell RNA sequencing and validation with in situ hybridization and immunofluorescence, we discovered that neo-angiogenesis is initiated specifically by venous endothelial cells during EAE. Moreover, we identified VEGF-A signaling as the primary driver of neo-angiogenesis in EAE, as treatment with the VEGF-A blocking antibody, bevacizumab, ameliorated the EAE pathology by reducing neo-angiogenesis in vivo. Our findings may lead to the development of novel therapeutics designed to reduce neo-angiogenesis and improve long-term neurological deficits in MS.

2023-03-14 | GSE210776 | GEO

COCO/DAND5 inhibits developmental and pathological ocular angiogenesis

Project description:COCO/DAND5 inhibits developmental and pathological ocular angiogenesis

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Oxygen-induced pathological angiogenesis promotes intense lipid synthesis and remodeling in the retina

Project description:<p>The retina is a notable tissue with high metabolic needs which relies on specialized vascular networks to protect the neural retina while maintaining constant supplies of oxygen, nutrients and dietary essential fatty acids. Here we analyzed the lipidome of the mouse retina under healthy and pathological angiogenesis using the oxygen-induced retinopathy model. By matching lipid profiles to changes in mRNA transcriptome, we identified a lipid signature showing that pathological angiogenesis leads to intense lipid remodeling favoring pathways for neutral lipid synthesis, cholesterol import/export and lipid droplet formation. Noteworthy, it also shows profound changes in pathways for long-chain fatty acid production, vital for retina homeostasis. The net result is accumulation of large quantities of mead acid, a marker of essential fatty acid deficiency, and a potential marker for retinopathy severity. Thus, our lipid signature might contribute to better understand diseases of the retina that lead to vision impairment or blindness.</p>

2023-05-09 | MTBLS6965 | MetaboLights

COCO/DAND5 inhibits developmental and pathological ocular angiogenesis

Project description:Neovascularization contributes to multiple visual disorders including age-related macular degeneration (AMD). Current therapies for treating ocular angiogenesis are centered on the inhibition of vascular endothelial growth factor (VEGF). While clinically effective, some AMD patients are refractory or develop resistance to anti-VEGF and concerns of increased risks of developing geographic atrophy following long-term treatment have been raised. Identification of alternative pathways to inhibit pathological angiogenesis is thus important. We have identified a novel inhibitor of angiogenesis, COCO/DAND5, a member of the Cerberus-related DAN family. We demonstrate that COCO inhibits sprouting, migration and cellular proliferation of cultured endothelial cells. Intravitreal injections of COCO inhibited retinal vascularization during development and in models of retinopathy of prematurity and AMD. COCO equally abrogated angiogenesis in choroid explants and in a model of choroidal neovascularization. Mechanistically, COCO inhibited the expression of TGFβ and BMP pathwaysand altered ATP production, glucose uptake and redox balance of endothelial cells. Together, these data show that COCO is an inhibitor of retinal and choroidal angiogenesis, possibly representing a therapeutic option for the treatment of neovascular ocular diseases.

2020-12-22 | GSE160099 | GEO

Identifying and targeting angiogenesis-related microRNAs in ovarian cancer

Project description:Identifying and targeting angiogenesis-related microRNAs in ovarian cancer

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Molecular markers in the CSF proteome differentiate neuroinflammatory diseases

2021-02-22 | PXD017643 | Pride

Endothelial cell heterogeneity in pathological angiogenesis characterized by metabolic transcriptome diversity

Project description:Endothelial cell heterogeneity in pathological angiogenesis characterized by metabolic transcriptome diversity

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Role of microRNA-143, -150 and 126 in pathological retinal angiogenesis

Project description:Role of microRNA-143, -150 and 126 in pathological retinal angiogenesis

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Endothelial cell heterogeneity in pathological angiogenesis characterized by metabolic transcriptome diversity

Project description:Endothelial cell heterogeneity in pathological angiogenesis characterized by metabolic transcriptome diversity

| PRJEB52990 | ENA

Molecular markers in the CSF proteome differentiate neuroinflammatory diseases

Project description:Manuscript "Molecular markers in the CSF proteome differentiate neuroinflammatory diseases" by Maria L. Elkjaer Arkadiusz Nawrocki, Tim Kacprowski, Anja Hviid Simonsen, Romain Marignier, Tobias Sejbaek, Helle H. Nielsen, Lene Wermuth, Peter Høgh, Finn Sellebjerg, Richard Reynolds, Jan Baumbach, Martin R. Larssen, Zsolt Illes (prepared for submission). Validation of differences in protein abundance, found in the discovery phase of the project (comparison of pools of respective samples), by analysis of proteomes of individual samples enrolled.

2022-08-08 | PXD017681 | Pride

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