Regulation of thrombin-mediated endothelial cell contraction and permeability

Joe G.N. Garcia, Alexander Dmitriyevich Verin, Kane L. Schaphorst

Research output: Contribution to journalReview article

103 Scopus citations

Abstract

A variety of physical forces exist in a dynamic equilibrium in the vascular endothelium (EC) monolayer and serve to maintain EC responsiveness while preserving the integrity of the EC monolayer and barrier properties. Thrombin has potent effects on EC permeabilities disrupting the equilibrium between tethering forces (cadherins, focal adhesion plaque) and forces that increase centripetal tension primarily via myosin light chain (MLC) phosphorylation. Like other EC effects, thrombin-induced MLC kinase (MLCK) activation is dependent upon receptor proteolysis, Ca2+ mobilization, and activation of protein kinase C (PKC). While EC gap formation is central to barrier dysfunction and dependent upon activation of MLCK, (which phosphorylates MLC) an obligatory event in smooth muscle cell contraction, little is known regarding the events that reverse inflammatory responses, halt the contractile response, and initiate relaxation. However, as these events likely include MLC dephosphorylation, further examination of the processes that regulate MLC protein phosphatase activity, focal intercellular junctions, and extracellular matrix adhesions is needed. These investigations should yield new information as to how receptor occupancy is transduced into specific cellular responses, such as increased permeability, which promotes pathological vascular processes such as tissue edema formation and organ dysfunction.

Original languageEnglish (US)
Pages (from-to)309-315
Number of pages7
JournalSeminars in Thrombosis and Hemostasis
Volume22
Issue number4
DOIs
Publication statusPublished - Jan 1 1996
Externally publishedYes

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Keywords

  • Focal adhesion kinase
  • Myosin light chain kinase
  • Permeability
  • Protein phosphatase
  • Thrombin

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

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