Title

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

Document Type

Journal Article

Publication Date

12-11-2012

Journal

Developmental cell

Volume

23

Issue

6

Inclusive Pages

1203–1218

DOI

10.1016/j.devcel.2012.11.003

Keywords

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

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.

Comments

This is an open access PubMed Central article.

Peer Reviewed

1

Open Access

1

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