title: Caveolae protect endothelial cells from membrane rupture during increased cardiac output.
abstract: Caveolae are strikingly abundant in endothelial cells, yet the physiological functions of caveolae in endothelium and other tissues remain incompletely understood. Previous studies suggest a mechanoprotective role, but whether this is relevant under the mechanical forces experienced by endothelial cells in vivo is unclear. In this study we have sought to determine whether endothelial caveolae disassemble under increased hemodynamic forces, and whether caveolae help prevent acute rupture of the plasma membrane under these conditions. Experiments in cultured cells established biochemical assays for disassembly of caveolar protein complexes, and assays for acute loss of plasma membrane integrity. In vivo, we demonstrate that caveolae in endothelial cells of the lung and cardiac muscle disassemble in response to acute increases in cardiac output. Electron microscopy and two-photon imaging reveal that the plasma membrane of microvascular endothelial cells in caveolin 1(-/-) mice is much more susceptible to acute rupture when cardiac output is increased. These data imply that mechanoprotection through disassembly of caveolae is important for endothelial function in vivo.
authors.affiliation: Medical Research Council, Laboratory of Molecular Biology, University of Cambridge, Cambridge CB2 1TN, UK.
authors.forename: Jade P X
authors.initials: JP
authors.lastname: Cheng
authors.affiliation: Medical Research Council, Laboratory of Molecular Biology, University of Cambridge, Cambridge CB2 1TN, UK.
authors.forename: Carolina
authors.initials: C
authors.lastname: Mendoza-Topaz
authors.affiliation: Medical Research Council, Laboratory of Molecular Biology, University of Cambridge, Cambridge CB2 1TN, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Howard
authors.affiliation: Medical Research Council, Laboratory of Molecular Biology, University of Cambridge, Cambridge CB2 1TN, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Chadwick
authors.affiliation: Medical Research Council, Laboratory of Molecular Biology, University of Cambridge, Cambridge CB2 1TN, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Shvets
authors.affiliation: Department of Physiology, University of Cambridge, Cambridge CB2 1TN, UK.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Cowburn
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge CB2 1TN, UK.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Dunmore
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge CB2 1TN, UK.
authors.forename: Alexi
authors.initials: A
authors.lastname: Crosby
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge CB2 1TN, UK.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Morrell
authors.affiliation: Medical Research Council, Laboratory of Molecular Biology, University of Cambridge, Cambridge CB2 1TN, UK ben@mrc-lmb.cam.ac.uk.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Nichols
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002302:Cardiac Output; D021941:Caveolae / Q000502:physiology*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D004705:Endocytosis; D042783:Endothelial Cells / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D051242:Caveolin 1