The Diaphragms of Fenestrated Endothelia: Gatekeepers of Vascular Permeability and Blood Composition

Autor: Randolph J. Noelle, Samantha Shipman, Marcus R. Luciano, Krishnamurthy V. Nemani, Raul Elgueta, Catherine Carrière, Karen L Moodie, Steven Fiering, Dan Tse, Nicole C. Smits, Barjor Gimi, Charles P. Daghlian, Hong-Kee Lee, Takashi Kobayashi, Sophie J. Deharvengt, Daniel S. Longnecker, Patricia Ernst, Radu V. Stan, Maarten Buitendijk, Caitlin L. McGarry, Nicholas W. Shworak, Alan R. Schned, Arief A. Suriawinata, Yan Xu
Rok vydání: 2012
Předmět:
Zdroj: 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, Fiering, S N, Noelle, R J, Gimi, B, Shworak, N W & 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
ISSN: 1534-5807
DOI: 10.1016/j.devcel.2012.11.003
Popis: 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.
Databáze: OpenAIRE