The role of plasmalemma vesicle-associated protein in pathological breakdown of blood-brain and blood-retinal barriers: potential novel therapeutic target for cerebral edema and diabetic macular edema.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_CC1CD9C0EB1E
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
The role of plasmalemma vesicle-associated protein in pathological breakdown of blood-brain and blood-retinal barriers: potential novel therapeutic target for cerebral edema and diabetic macular edema.
Journal
Fluids and barriers of the CNS
Author(s)
Bosma E.K., van Noorden CJF, Schlingemann R.O., Klaassen I.
ISSN
2045-8118 (Electronic)
ISSN-L
2045-8118
Publication state
Published
Issued date
20/09/2018
Peer-reviewed
Oui
Volume
15
Number
1
Pages
24
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: epublish
Abstract
Breakdown of the blood-brain barrier (BBB) or inner blood-retinal barrier (BRB), induced by pathologically elevated levels of vascular endothelial growth factor (VEGF) or other mediators, can lead to vasogenic edema and significant clinical problems such as neuronal morbidity and mortality, or vision loss. Restoration of the barrier function with corticosteroids in the brain, or by blocking VEGF in the eye are currently the predominant treatment options for brain edema and diabetic macular edema, respectively. However, corticosteroids have side effects, and VEGF has important neuroprotective, vascular protective and wound healing functions, implying that long-term anti-VEGF therapy may also induce adverse effects. We postulate that targeting downstream effector proteins of VEGF and other mediators that are directly involved in the regulation of BBB and BRB integrity provide more attractive and safer treatment options for vasogenic cerebral edema and diabetic macular edema. The endothelial cell-specific protein plasmalemma vesicle-associated protein (PLVAP), a protein associated with trans-endothelial transport, emerges as candidate for this approach. PLVAP is expressed in a subset of endothelial cells throughout the body where it forms the diaphragms of caveolae, fenestrae and trans-endothelial channels. However, PLVAP expression in brain and eye barrier endothelia only occurs in pathological conditions associated with a compromised barrier function such as cancer, ischemic stroke and diabetic retinopathy. Here, we discuss the current understanding of PLVAP as a structural component of endothelial cells and regulator of vascular permeability in health and central nervous system disease. Besides providing a perspective on PLVAP identification, structure and function, and the regulatory processes involved, we also explore its potential as a novel therapeutic target for vasogenic cerebral edema and retinal macular edema.
Keywords
Animals, Blood-Brain Barrier/metabolism, Blood-Brain Barrier/pathology, Blood-Retinal Barrier/metabolism, Blood-Retinal Barrier/pathology, Brain/metabolism, Brain Edema/metabolism, Brain Edema/pathology, Capillary Permeability, Carrier Proteins/metabolism, Diabetes Complications/metabolism, Diabetes Complications/pathology, Eye/metabolism, Humans, Macular Edema/complications, Macular Edema/metabolism, Macular Edema/pathology, Membrane Proteins/metabolism, Blood–brain barrier, Blood–retinal barrier, Cerebral edema, Diabetic macular edema, Plasmalemma vesicle-associated protein
Pubmed
Web of science
Open Access
Yes
Create date
08/10/2018 16:38
Last modification date
20/08/2019 15:46
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