Hyaluronidase-1-mediated glycocalyx impairment underlies endothelial abnormalities in polypoidal choroidal vasculopathy Article Swipe
Kan Xing Wu
,
Natalie Jia Ying Yeo
,
Chun‐Yi Ng
,
Florence Wen Jing Chioh
,
Qiao Fan
,
Xianfeng Tian
,
Binxia Yang
,
Gunaseelan Narayanan
,
Hui-Min Tay
,
Han-Wei Hou
,
N. Ray Dunn
,
Xinyi Su
,
Chui Ming Gemmy Cheung
,
Christine Cheung
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.10.06.463357
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.10.06.463357
Background Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD), is characterized by polyp-like dilatation of blood vessels and turbulent blood flow in the choroid of the eye. Gold standard anti-vascular endothelial growth factor (anti-VEGF) therapy often fails to regress polypoidal lesions in patients. Current animal models have also been hampered by their inability to recapitulate such vascular lesions. These underscore the need to identify VEGF-independent pathways in PCV pathogenesis. Results We cultivated blood outgrowth endothelial cells (BOECs) from PCV patients and normal controls to serve as our experimental disease models. When BOECs were exposed to heterogeneous flow, single-cell transcriptomic analysis revealed that PCV BOECs preferentially adopted migratory-angiogenic cell state, while normal BOECs undertook proinflammatory cell state. PCV BOECs also had a repressed protective response to flow stress by demonstrating lower mitochondrial functions. We uncovered that elevated hyaluronidase-1 in PCV BOECs led to increased degradation of hyaluronan, a major component of glycocalyx that interfaces between flow stress and vascular endothelium. Notably, knockdown of hyaluronidase-1 in PCV BOEC improved mechanosensitivity through activation of Krüppel-like factor 2, a flow-responsive transcription factor, which in turn modulated PCV BOEC migration. Barrier permeability due to glycocalyx impairment in PCV BOECs was also reversed by hyaluronidase-1 knockdown. Correspondingly, hyaluronidase-1 was detected in PCV patient vitreous humor and plasma samples. Conclusions Hyaluronidase-1 inhibition could be a potential therapeutic modality in preserving glycocalyx integrity and endothelial stability in ocular diseases with vascular origin.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2021.10.06.463357
- https://www.biorxiv.org/content/biorxiv/early/2021/10/07/2021.10.06.463357.full.pdf
- OA Status
- green
- References
- 86
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3203427050
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3203427050Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2021.10.06.463357Digital Object Identifier
- Title
-
Hyaluronidase-1-mediated glycocalyx impairment underlies endothelial abnormalities in polypoidal choroidal vasculopathyWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-10-07Full publication date if available
- Authors
-
Kan Xing Wu, Natalie Jia Ying Yeo, Chun‐Yi Ng, Florence Wen Jing Chioh, Qiao Fan, Xianfeng Tian, Binxia Yang, Gunaseelan Narayanan, Hui-Min Tay, Han-Wei Hou, N. Ray Dunn, Xinyi Su, Chui Ming Gemmy Cheung, Christine CheungList of authors in order
- Landing page
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https://doi.org/10.1101/2021.10.06.463357Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2021/10/07/2021.10.06.463357.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2021/10/07/2021.10.06.463357.full.pdfDirect OA link when available
- Concepts
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Glycocalyx, Hyaluronidase, Vascular endothelial growth factor, Choroid, Medicine, Macular degeneration, Cancer research, Pathology, Biology, Immunology, Retina, VEGF receptors, Ophthalmology, Enzyme, Neuroscience, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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86Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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