The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition

Radu V Stan; Dan Tse; Sophie J Deharvengt; Nicole C Smits; Yan Xu; Marcus R Luciano; Caitlin L McGarry; Maarten Buitendijk; Krishnamurthy V Nemani; Raul Elgueta; Takashi Kobayashi; Samantha L Shipman; Karen L Moodie; Charles P Daghlian; Patricia A Ernst; Hong-Kee Lee; Arief A Suriawinata; Alan R Schned; Daniel S Longnecker; Steven N Fiering; Randolph J Noelle; Barjor Gimi; Nicholas W Shworak; Catherine Carrière

doi:10.1016/j.devcel.2012.11.003

The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition

Radu V Stan, Dan Tse, Sophie J Deharvengt, Nicole C Smits, Yan Xu, Marcus R Luciano, Caitlin L McGarry, Maarten Buitendijk, Krishnamurthy V Nemani, Raul Elgueta, Takashi Kobayashi, Samantha L Shipman, Karen L Moodie, Charles P Daghlian, Patricia A Ernst, Hong-Kee Lee, Arief A Suriawinata, Alan R Schned, Daniel S Longnecker, Steven N FieringRandolph J Noelle, Barjor Gimi, Nicholas W Shworak, Catherine Carrière

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Abstract

Fenestral and stomatal diaphragms are endothelial subcellular structures of unknown function that form on organelles implicated in vascular permeability: fenestrae, transendothelial channels, and caveolae. PV1 protein is required for diaphragm formation in vitro. Here, we report that deletion of the PV1-encoding Plvap gene in mice results in the absence of diaphragms and decreased survival. Loss of diaphragms did not affect the fenestrae and transendothelial channels formation but disrupted the barrier function of fenestrated capillaries, causing a major leak of plasma proteins. This disruption results in early death of animals due to severe noninflammatory protein-losing enteropathy. Deletion of PV1 in endothelium, but not in the hematopoietic compartment, recapitulates the phenotype of global PV1 deletion, whereas endothelial reconstitution of PV1 rescues the phenotype. Taken together, these data provide genetic evidence for the critical role of the diaphragms in fenestrated capillaries in the maintenance of blood composition.

Original language	English
Pages (from-to)	1203-18
Number of pages	16
Journal	Developmental Cell
Volume	23
Issue number	6
DOIs	https://doi.org/10.1016/j.devcel.2012.11.003
Publication status	Published - 11 Dec 2012

Keywords

Animals
Blood Proteins
Capillaries
Capillary Permeability
Carrier Proteins
Caveolae
Cell Membrane
Endothelium, Vascular
Membrane Proteins
Mice
Mice, Transgenic
Protein-Losing Enteropathies

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10.1016/j.devcel.2012.11.003

The diaphragms of fenestrated endothelia gatekeepers of vascular permeability and blood composition AAMAccepted author manuscript, 5.37 MBLicence: CC BY-NC-ND

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Stan, R. V., Tse, D., Deharvengt, S. J., Smits, N. C., Xu, Y., Luciano, M. R., McGarry, C. L., Buitendijk, M., Nemani, K. V., Elgueta, R., Kobayashi, T., Shipman, S. L., Moodie, K. L., Daghlian, C. P., Ernst, P. A., Lee, H.-K., Suriawinata, A. A., Schned, A. R., Longnecker, D. S., ... Carrière, C. (2012). The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition. Developmental Cell, 23(6), 1203-18. https://doi.org/10.1016/j.devcel.2012.11.003

@article{7aa78025d8884a4b9b4bfb2d3fb439ee,

title = "The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition",

abstract = "Fenestral and stomatal diaphragms are endothelial subcellular structures of unknown function that form on organelles implicated in vascular permeability: fenestrae, transendothelial channels, and caveolae. PV1 protein is required for diaphragm formation in vitro. Here, we report that deletion of the PV1-encoding Plvap gene in mice results in the absence of diaphragms and decreased survival. Loss of diaphragms did not affect the fenestrae and transendothelial channels formation but disrupted the barrier function of fenestrated capillaries, causing a major leak of plasma proteins. This disruption results in early death of animals due to severe noninflammatory protein-losing enteropathy. Deletion of PV1 in endothelium, but not in the hematopoietic compartment, recapitulates the phenotype of global PV1 deletion, whereas endothelial reconstitution of PV1 rescues the phenotype. Taken together, these data provide genetic evidence for the critical role of the diaphragms in fenestrated capillaries in the maintenance of blood composition.",

keywords = "Animals, Blood Proteins, Capillaries, Capillary Permeability, Carrier Proteins, Caveolae, Cell Membrane, Endothelium, Vascular, Membrane Proteins, Mice, Mice, Transgenic, Protein-Losing Enteropathies",

author = "Stan, {Radu V} and Dan Tse and Deharvengt, {Sophie J} and Smits, {Nicole C} and Yan Xu and Luciano, {Marcus R} and McGarry, {Caitlin L} and Maarten Buitendijk and Nemani, {Krishnamurthy V} and Raul Elgueta and Takashi Kobayashi and Shipman, {Samantha L} and Moodie, {Karen L} and Daghlian, {Charles P} and Ernst, {Patricia A} and Hong-Kee Lee and Suriawinata, {Arief A} and Schned, {Alan R} and Longnecker, {Daniel S} and Fiering, {Steven N} and Noelle, {Randolph J} and Barjor Gimi and Shworak, {Nicholas W} and Catherine Carri{\`e}re",

year = "2012",

month = dec,

day = "11",

doi = "10.1016/j.devcel.2012.11.003",

language = "English",

volume = "23",

pages = "1203--18",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "6",

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Stan, RV, Tse, D, Deharvengt, SJ, Smits, NC, Xu, Y, Luciano, MR, McGarry, CL, Buitendijk, M, Nemani, KV, Elgueta, R, Kobayashi, T, Shipman, SL, Moodie, KL, Daghlian, CP, Ernst, PA, Lee, H-K, Suriawinata, AA, Schned, AR, Longnecker, DS, Fiering, SN, Noelle, RJ, Gimi, B, Shworak, NW & Carrière, C 2012, 'The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition', Developmental Cell, vol. 23, no. 6, pp. 1203-18. https://doi.org/10.1016/j.devcel.2012.11.003

TY - JOUR

T1 - The diaphragms of fenestrated endothelia

T2 - gatekeepers of vascular permeability and blood composition

AU - Stan, Radu V

AU - Tse, Dan

AU - Deharvengt, Sophie J

AU - Smits, Nicole C

AU - Xu, Yan

AU - Luciano, Marcus R

AU - McGarry, Caitlin L

AU - Buitendijk, Maarten

AU - Nemani, Krishnamurthy V

AU - Elgueta, Raul

AU - Kobayashi, Takashi

AU - Shipman, Samantha L

AU - Moodie, Karen L

AU - Daghlian, Charles P

AU - Ernst, Patricia A

AU - Lee, Hong-Kee

AU - Suriawinata, Arief A

AU - Schned, Alan R

AU - Longnecker, Daniel S

AU - Fiering, Steven N

AU - Noelle, Randolph J

AU - Gimi, Barjor

AU - Shworak, Nicholas W

AU - Carrière, Catherine

PY - 2012/12/11

Y1 - 2012/12/11

N2 - Fenestral and stomatal diaphragms are endothelial subcellular structures of unknown function that form on organelles implicated in vascular permeability: fenestrae, transendothelial channels, and caveolae. PV1 protein is required for diaphragm formation in vitro. Here, we report that deletion of the PV1-encoding Plvap gene in mice results in the absence of diaphragms and decreased survival. Loss of diaphragms did not affect the fenestrae and transendothelial channels formation but disrupted the barrier function of fenestrated capillaries, causing a major leak of plasma proteins. This disruption results in early death of animals due to severe noninflammatory protein-losing enteropathy. Deletion of PV1 in endothelium, but not in the hematopoietic compartment, recapitulates the phenotype of global PV1 deletion, whereas endothelial reconstitution of PV1 rescues the phenotype. Taken together, these data provide genetic evidence for the critical role of the diaphragms in fenestrated capillaries in the maintenance of blood composition.

AB - Fenestral and stomatal diaphragms are endothelial subcellular structures of unknown function that form on organelles implicated in vascular permeability: fenestrae, transendothelial channels, and caveolae. PV1 protein is required for diaphragm formation in vitro. Here, we report that deletion of the PV1-encoding Plvap gene in mice results in the absence of diaphragms and decreased survival. Loss of diaphragms did not affect the fenestrae and transendothelial channels formation but disrupted the barrier function of fenestrated capillaries, causing a major leak of plasma proteins. This disruption results in early death of animals due to severe noninflammatory protein-losing enteropathy. Deletion of PV1 in endothelium, but not in the hematopoietic compartment, recapitulates the phenotype of global PV1 deletion, whereas endothelial reconstitution of PV1 rescues the phenotype. Taken together, these data provide genetic evidence for the critical role of the diaphragms in fenestrated capillaries in the maintenance of blood composition.

KW - Animals

KW - Blood Proteins

KW - Capillaries

KW - Capillary Permeability

KW - Carrier Proteins

KW - Caveolae

KW - Cell Membrane

KW - Endothelium, Vascular

KW - Membrane Proteins

KW - Mice

KW - Mice, Transgenic

KW - Protein-Losing Enteropathies

U2 - 10.1016/j.devcel.2012.11.003

DO - 10.1016/j.devcel.2012.11.003

M3 - Article

C2 - 23237953

SN - 1534-5807

VL - 23

SP - 1203

EP - 1218

JO - Developmental Cell

JF - Developmental Cell

IS - 6

ER -

The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition

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