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.
authors.affiliation: Department of Pathology, Geisel School of Medicine at Dartmouth, Hanover, NH 03756, USA. radu.v.stan@dartmouth.edu
authors.forename: Radu V
authors.initials: RV
authors.lastname: Stan
authors.forename: Dan
authors.initials: D
authors.lastname: Tse
authors.forename: Sophie J
authors.initials: SJ
authors.lastname: Deharvengt
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Smits
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Luciano
authors.forename: Caitlin L
authors.initials: CL
authors.lastname: McGarry
authors.forename: Maarten
authors.initials: M
authors.lastname: Buitendijk
authors.forename: Krishnamurthy V
authors.initials: KV
authors.lastname: Nemani
authors.forename: Raul
authors.initials: R
authors.lastname: Elgueta
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Shipman
authors.forename: Karen L
authors.initials: KL
authors.lastname: Moodie
authors.forename: Charles P
authors.initials: CP
authors.lastname: Daghlian
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ernst
authors.forename: Hong-Kee
authors.initials: HK
authors.lastname: Lee
authors.forename: Arief A
authors.initials: AA
authors.lastname: Suriawinata
authors.forename: Alan R
authors.initials: AR
authors.lastname: Schned
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Longnecker
authors.forename: Steven N
authors.initials: SN
authors.lastname: Fiering
authors.forename: Randolph J
authors.initials: RJ
authors.lastname: Noelle
authors.forename: Barjor
authors.initials: B
authors.lastname: Gimi
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Shworak
authors.forename: Catherine
authors.initials: C
authors.lastname: Carrière
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002196:Capillaries / Q000502:physiology* / Q000648:ultrastructure*; D002199:Capillary Permeability; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D021941:Caveolae / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011504:Protein-Losing Enteropathies / Q000503:physiopathology
chemical_list: D001798:Blood Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; C486772:Plvap protein, mouse