Single-cell RNA-sequencing implicates venous endothelial cells as a source of VEGF-A-mediated neo-angiogenesis in neuroinflammation Article Swipe

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Sanjid Shahriar , Saptarshi Biswas , Kuaile Zhao , Uğur Akcan , Mary Claire Tuohy , Michael Glendinning , Anne-Marie Kurt , Charlotte R. Wayne , Grace Prochilo , Marvin Price , Rolf A. Brekken , Vilas Menon , Dritan Agalliu ·

YOU? · · 2022 · Open Access · · DOI: https://doi.org/10.1101/2022.11.15.516660

Histopathological studies of multiple sclerosis (MS), a demyelinating disease of the central nervous system (CNS), and its animal model, experimental autoimmune encephalomyelitis (EAE), have found newly formed leaky vessels in demyelinated acute and chronic plaques, in addition to blood-brain barrier (BBB) damage in existing vessels, that exacerbate disease pathology by increasing infiltration of immune cells. Which vessel subtypes and signaling pathways generate these aberrant vessels is poorly understood. Using single-cell RNA-sequencing and in vivo validation, we find that transcriptome signatures of neo-angiogenesis arise in venous endothelial cells in both acute and chronic EAE, and correlate with upregulation in VEGF-A signaling. These neo-angiogenic markers are also increased in acute and chronic MS lesions. Treatment with a VEGF-A blocking antibody diminishes neo-angiogenic transcriptomic signatures and vascular proliferation in vivo , but does not restore BBB function or ameliorate significantly EAE pathology. Therefore, anti-angiogenic therapies in combination with immunomodulatory therapies may benefit MS progression.

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Experimental autoimmune encephalomyelitis Angiogenesis Neuroinflammation Multiple sclerosis Transcriptome Vascular endothelial growth factor Neovascularization Glioma Immune system Microglia Immunology Pathology Cancer research In vivo Encephalomyelitis Medicine Biology Inflammation VEGF receptors Gene expression Biotechnology Biochemistry Gene

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1101/2022.11.15.516660
PDF: https://www.biorxiv.org/content/biorxiv/early/2022/11/15/2022.11.15.516660.full.pdf
OA Status: green
Cited By: 3
References: 106
Related Works: 10
OpenAlex ID: https://openalex.org/W4309400995

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DOI: https://doi.org/10.1101/2022.11.15.516660

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Title: Single-cell RNA-sequencing implicates venous endothelial cells as a source of VEGF-A-mediated neo-angiogenesis in neuroinflammation

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Type: preprint

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Language: en

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Publication year: 2022

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Publication date: 2022-11-15

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Authors: Sanjid Shahriar, Saptarshi Biswas, Kuaile Zhao, Uğur Akcan, Mary Claire Tuohy, Michael Glendinning, Anne-Marie Kurt, Charlotte R. Wayne, Grace Prochilo, Marvin Price, Rolf A. Brekken, Vilas Menon, Dritan Agalliu

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Landing page: https://doi.org/10.1101/2022.11.15.516660

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PDF URL: https://www.biorxiv.org/content/biorxiv/early/2022/11/15/2022.11.15.516660.full.pdf

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Concepts: Experimental autoimmune encephalomyelitis, Angiogenesis, Neuroinflammation, Multiple sclerosis, Transcriptome, Vascular endothelial growth factor, Neovascularization, Glioma, Immune system, Microglia, Immunology, Pathology, Cancer research, In vivo, Encephalomyelitis, Medicine, Biology, Inflammation, VEGF receptors, Gene expression, Biotechnology, Biochemistry, Gene

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Cited by: 3

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Citations by year (recent): 2025: 2, 2023: 1

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