Recombinant PAI-1 therapy restores myoendothelial junctions and erectile function in PAI-1-deficient mice

Summary 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...

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Bibliographic Details
Published in:Andrologia 2015-12, Vol.47 (10), p.1147-1152
Main Authors: Kavoussi, P. K., Heberlein, K., Straub, A. C., Lowe, G. J., Oliver, J. L., Smith, R. P., Steers, W. D., Annex, B. H., Isakson, B. E., Lysiak, J. J.
Format: Article
Language:English
Subjects:
Animals
Cell Communication
endothelial cells
Endothelium, Vascular - drug effects
Endothelium, Vascular - physiology
Endothelium, Vascular - ultrastructure
erectile dysfunction
Erectile Dysfunction - drug therapy
Erectile Dysfunction - etiology
Intercellular Junctions - drug effects
Intercellular Junctions - physiology
Intercellular Junctions - ultrastructure
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Electron, Transmission
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - physiology
Muscle, Smooth, Vascular - ultrastructure
Penile Erection - drug effects
plasminogen activators
Recombinant Proteins
Serpin E2 - deficiency
Serpin E2 - therapeutic use
vascular smooth muscle
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Summary:Summary 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.
ISSN:0303-4569
1439-0272
DOI:10.1111/and.12395