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Review ArticleReview Article

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

Marie Billaud, Alexander W. Lohman, Scott R. Johnstone, Lauren A. Biwer, Stephanie Mutchler and Brant E. Isakson
Christopher J. Garland, ASSOCIATE EDITOR
Pharmacological Reviews April 2014, 66 (2) 513-569; DOI: https://doi.org/10.1124/pr.112.007351
Marie Billaud
Department of Molecular Physiology and Biophysics (M.B., A.W.L, L.A.B., B.E.I.) and Robert M Berne Cardiovascular Research Center (M.B., A.W.L., L.A.B., S.M., B.E.I.), University of Virginia School of Medicine, Charlottesville, Virginia; and Institute of Cardiovascular & Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.R.J.)
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Alexander W. Lohman
Department of Molecular Physiology and Biophysics (M.B., A.W.L, L.A.B., B.E.I.) and Robert M Berne Cardiovascular Research Center (M.B., A.W.L., L.A.B., S.M., B.E.I.), University of Virginia School of Medicine, Charlottesville, Virginia; and Institute of Cardiovascular & Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.R.J.)
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Scott R. Johnstone
Department of Molecular Physiology and Biophysics (M.B., A.W.L, L.A.B., B.E.I.) and Robert M Berne Cardiovascular Research Center (M.B., A.W.L., L.A.B., S.M., B.E.I.), University of Virginia School of Medicine, Charlottesville, Virginia; and Institute of Cardiovascular & Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.R.J.)
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Lauren A. Biwer
Department of Molecular Physiology and Biophysics (M.B., A.W.L, L.A.B., B.E.I.) and Robert M Berne Cardiovascular Research Center (M.B., A.W.L., L.A.B., S.M., B.E.I.), University of Virginia School of Medicine, Charlottesville, Virginia; and Institute of Cardiovascular & Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.R.J.)
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Stephanie Mutchler
Department of Molecular Physiology and Biophysics (M.B., A.W.L, L.A.B., B.E.I.) and Robert M Berne Cardiovascular Research Center (M.B., A.W.L., L.A.B., S.M., B.E.I.), University of Virginia School of Medicine, Charlottesville, Virginia; and Institute of Cardiovascular & Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.R.J.)
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Brant E. Isakson
Department of Molecular Physiology and Biophysics (M.B., A.W.L, L.A.B., B.E.I.) and Robert M Berne Cardiovascular Research Center (M.B., A.W.L., L.A.B., S.M., B.E.I.), University of Virginia School of Medicine, Charlottesville, Virginia; and Institute of Cardiovascular & Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.R.J.)
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Christopher J. Garland
Department of Molecular Physiology and Biophysics (M.B., A.W.L, L.A.B., B.E.I.) and Robert M Berne Cardiovascular Research Center (M.B., A.W.L., L.A.B., S.M., B.E.I.), University of Virginia School of Medicine, Charlottesville, Virginia; and Institute of Cardiovascular & Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.R.J.)
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Abstract

It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function.

Footnotes

  • This work was supported by National Institutes of Health National Heart, Lung, and Blood Institute [Grants HL088554 (to B.E.I.) and HL107963 (to B.E.I.)]; and an American Heart Association predoctoral fellowship (to A.W.L.).

  • dx.doi.org/10.1124/pr.112.007351.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 66 (2)
Pharmacological Reviews
Vol. 66, Issue 2
1 Apr 2014
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Review ArticleReview Article

Regulation of Cellular Communication in Blood Vessel Wall

Marie Billaud, Alexander W. Lohman, Scott R. Johnstone, Lauren A. Biwer, Stephanie Mutchler and Brant E. Isakson
Pharmacological Reviews April 1, 2014, 66 (2) 513-569; DOI: https://doi.org/10.1124/pr.112.007351

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Review ArticleReview Article

Regulation of Cellular Communication in Blood Vessel Wall

Marie Billaud, Alexander W. Lohman, Scott R. Johnstone, Lauren A. Biwer, Stephanie Mutchler and Brant E. Isakson
Pharmacological Reviews April 1, 2014, 66 (2) 513-569; DOI: https://doi.org/10.1124/pr.112.007351
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  • Article
    • Abstract
    • I. Introduction
    • II. Gaseous Molecule Cellular Communication by Signaling Microdomains
    • III. Channel-Based Cellular Communication by Signaling Microdomains
    • IV. Vesicular Communication: The Exocytosis Microdomain
    • V. Conclusion
    • Acknowledgments
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