title: Recombinant PAI-1 therapy restores myoendothelial junctions and erectile function in PAI-1-deficient mice.
abstract: Myoendothelial junctions are specialised projections of cell : cell contact through the internal elastic lamina between endothelial cells and vascular smooth muscle cells. These junctions allow for endothelial cells and vascular smooth muscle cells to make direct membrane apposition and are involved in cell : cell communication. In this study, we evaluated for the presence of myoendothelial junctions in murine corporal tissue and used plasminogen activator inhibitor (PAI)-1-deficient mice, which lack myoendothelial junctions, to determine whether myoendothelial junctions affect erectile function. Transmission electron microscopy demonstrated the presence of myoendothelial junctions in the corporal tissue of wild-type mice and confirmed the decreased junction numbers in the tissue of PAI-1(-/-) mice. A potential role for myoendothelial junctions in tumescence was established; in that, PAI-1(-/-) mice demonstrated a significantly longer time to achieve maximal intracavernous pressure. Treatment of PAI-1(-/-) mice with recombinant PAI-1 restored the number of myoendothelial junctions in the corporal tissue and also induced a significant decrease in time to maximal corporal pressures. Myoendothelial junctions were similarly identified in the human corporal tissue. These results suggest a critical role for myoendothelial junctions in erectile pathophysiology and therapies aimed at restoring myoendothelial junction numbers in the corporal tissue may provide a novel therapy for erectile dysfunction.
authors.affiliation: Department of Urology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Kavoussi
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Heberlein
authors.affiliation: Robert M. Berne Cardiovascular Research Center, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Straub
authors.affiliation: Department of Urology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Lowe
authors.affiliation: Department of Urology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Oliver
authors.affiliation: Department of Urology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Smith
authors.affiliation: Department of Urology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: Steers
authors.affiliation: Robert M. Berne Cardiovascular Research Center, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Annex
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, VA, USA.|Robert M. Berne Cardiovascular Research Center, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Isakson
authors.affiliation: Department of Urology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lysiak
mesh_terms: D000818:Animals; D002450:Cell Communication; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology; D007365:Intercellular Junctions / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D010410:Penile Erection / Q000187:drug effects*; D011994:Recombinant Proteins; D058258:Serpin E2 / Q000172:deficiency* / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D058258:Serpin E2; C511869:Serpine2 protein, mouse
keywords: Cell communication; endothelial cells; erectile dysfunction; plasminogen activators; vascular smooth muscle