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Molecular mechanisms of endothelial hyperpermeability: implications in inflammation

Published online by Cambridge University Press:  30 June 2009

Puneet Kumar ,
Qiang Shen ,
Christopher D. Pivetti ,
Eugene S. Lee ,
Mack H. Wu  and
Sarah Y. Yuan
Puneet Kumar
Affiliation:
Division of Research, Department of Surgery, University of California at Davis School of Medicine, Sacramento, CA 95758, USA.
Qiang Shen
Affiliation:
Division of Research, Department of Surgery, University of California at Davis School of Medicine, Sacramento, CA 95758, USA.
Christopher D. Pivetti
Affiliation:
Division of Research, Department of Surgery, University of California at Davis School of Medicine, Sacramento, CA 95758, USA.
Eugene S. Lee
Affiliation:
Division of Research, Department of Surgery, University of California at Davis School of Medicine, Sacramento, CA 95758, USA.
Mack H. Wu
Affiliation:
Division of Research, Department of Surgery, University of California at Davis School of Medicine, Sacramento, CA 95758, USA.
Sarah Y. Yuan*
Affiliation:
Division of Research, Department of Surgery, University of California at Davis School of Medicine, Sacramento, CA 95758, USA.
*
*Corresponding author: Sarah Yuan, Department of Surgery, University of California Davis Medical Center, 4625 2nd Avenue, Room 3006, Sacramento, CA 95817, USA. Tel: +1 916 703 0422; Fax: +1 916 703 0421; E-mail: [email protected]
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Abstract

Endothelial hyperpermeability is a significant problem in vascular inflammation associated with trauma, ischaemia–reperfusion injury, sepsis, adult respiratory distress syndrome, diabetes, thrombosis and cancer. An important mechanism underlying this process is increased paracellular leakage of plasma fluid and protein. Inflammatory stimuli such as histamine, thrombin, vascular endothelial growth factor and activated neutrophils can cause dissociation of cell–cell junctions between endothelial cells as well as cytoskeleton contraction, leading to a widened intercellular space that facilitates transendothelial flux. Such structural changes initiate with agonist–receptor binding, followed by activation of intracellular signalling molecules including calcium, protein kinase C, tyrosine kinases, myosin light chain kinase, and small Rho-GTPases; these kinases and GTPases then phosphorylate or alter the conformation of different subcellular components that control cell–cell adhesion, resulting in paracellular hypermeability. Targeting key signalling molecules that mediate endothelial-junction–cytoskeleton dissociation demonstrates a therapeutic potential to improve vascular barrier function during inflammatory injury.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e19
Copyright
Copyright © Cambridge University Press 2009

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References

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Further reading, resources and contacts

Mammoto, A. et al. (2008) Rho signaling and mechanical control of vascular development. Vascular Biology 15, 228-234Google ScholarPubMed
van Nieuw Amerongen, G.P. et al. (2003) Targets for pharmacological intervention of endothelial hyperpermeability and barrier function. Vascular Pharmacology 39, 257-272CrossRefGoogle Scholar
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