Plasmalemmal Vesicle Associated Protein-1 (PV-1) is a marker of blood-brain barrier disruption in rodent models

Shue, Eveline; Carson-Walter, Eleanor B.; Liu, Yang; Winans, Bethany; Ali, Zarina S.; Chen, Jun; Walter, Kevin A.

doi:10.1186/1471-2202-9-29

Cited by 94 publications

(90 citation statements)

References 24 publications

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“…Upregulation of PV-1 in the brain vasculature during BBB disruption in rodents has already been demonstrated (Shue et al, 2008). Our finding that increased blood content of Fg causes greater formation of PV-1 in WT than in MMP9À/À mice indicates that at high level, Fg may enhance a transendothelial transport through activation of MMP-9.…”

Section: Discussionsupporting

confidence: 68%

Fibrinogen-Induced Increased Pial Venular Permeability in Mice

Muradashvili

Qipshidze

Munjal

et al. 2011

J Cereb Blood Flow Metab

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Elevated blood level of Fibrinogen (Fg) is commonly associated with vascular dysfunction. We tested the hypothesis that at pathologically high levels, Fg increases cerebrovascular permeability by activating matrix metalloproteinases (MMPs). Fibrinogen (4 mg/mL blood concentration) or equal volume of phosphate-buffered saline (PBS) was infused into male wild-type (WT; C57BL/6J) or MMP-9 gene knockout (MMP9À/À) mice. Pial venular leakage of fluorescein isothiocyanate-bovine serum albumin to Fg or PBS alone and to topically applied histamine (10 À5 mol/L) were assessed. Intravital fluorescence microscopy and image analysis were used to assess cerebrovascular protein leakage. Pial venular macromolecular leakage increased more after Fg infusion than after infusion of PBS in both (WT and MMP9À/À) mice but was more pronounced in WT compared with MMP9À/À mice. Expression of vascular endothelial cadherin (VE-cadherin) was less and plasmalemmal vesicle-associated protein-1 (PV-1) was greater in Fg-infused than in PBS-infused both mice groups. However, in MMP9À/À mice, VE-cadherin expression was greater and PV-1 expression was less than in WT mice. These data indicate that at higher levels, Fg compromises microvascular integrity through activation of MMP-9 and downregulation of VE-cadherin and upregulation of PV-1. Our results suggest that elevated blood level of Fg could have a significant role in cerebrovascular dysfunction and remodeling.

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Section: Discussionsupporting

confidence: 68%

Fibrinogen-Induced Increased Pial Venular Permeability in Mice

Muradashvili

Qipshidze

Munjal

et al. 2011

J Cereb Blood Flow Metab

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“…Plasmalemma vesicle-associated protein (PLVAP) expression is enriched in peripheral ECs compared with CNS ECs, and has been implicated in vesicle trafficking, formation of fenestra, and leukocyte extravasation in these "leaky" vascular beds. This molecule is also up-regulated in CNS ECs in a variety of diseases in which there is BBB leakage (Shue et al 2008;Keuschnigg et al 2009). Therefore, lack of PLVAP in healthy CNS ECs appears to be important for limiting permeability.…”

Section: Transcytosismentioning

confidence: 99%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

2,399

1,829

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Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

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“…S9 A and B). We also evaluated expression of plasmalemma vesicle-associated protein (PLVAP), a marker of stomatal and fenestral diaphragms that is normally silenced with tightening of the BBB and absent from mature CNS vasculature (25)(26)(27)(28). By E13.5, PLVAP was absent from WT vessels but was readily detected in the abnormal vessels of Gpr124 −/− brains (Fig.…”

Section: Gpr124mentioning

confidence: 99%

GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood–brain barrier

Cullen

ElZarrad

Seaman

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

171

179

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Every organ in the body requires blood vessels for efficient delivery of oxygen and nutrients, but independent vascular beds are highly specialized to meet the individual needs of specific organs. The vasculature of the brain is tightly sealed, with bloodbrain barrier (BBB) properties developing coincident with neural vascularization. G protein-coupled receptor 124 (GPR124) (tumor endothelial marker 5, TEM5), an orphan member of the adhesion family of G protein-coupled receptors, was previously identified on the basis of its overexpression in tumor vasculature. Here, we show that global deletion or endothelial-specific deletion of GPR124 in mice results in embryonic lethality associated with abnormal angiogenesis of the forebrain and spinal cord. Expression of GPR124 was found to be required for invasion and migration of blood vessels into neuroepithelium, establishment of BBB properties, and expansion of the cerebral cortex. Thus, GPR124 is an important regulator of neurovasculature development and a potential drug target for cerebrovascular diseases.

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Plasmalemmal Vesicle Associated Protein-1 (PV-1) is a marker of blood-brain barrier disruption in rodent models

Cited by 94 publications

References 24 publications

Fibrinogen-Induced Increased Pial Venular Permeability in Mice

Fibrinogen-Induced Increased Pial Venular Permeability in Mice

The Blood–Brain Barrier

GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood–brain barrier

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