Differential role of Rho GTPases in endothelial barrier regulation dependent on endothelial cell origin

Y. Baumer, S. Burger, F. E. Curry, N. Golenhofen, D. Drenckhahn, J. Waschke

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


From studies using macrovascular endothelium, it was concluded that Rho A activation generally leads to endothelial barrier breakdown. Here, we characterized the role of Rho GTPases in endothelial barrier regulation in four different cell lines, both microvascular and macrovascular. Rho A activation by cytotoxic necrotizing factor y (CNFy) induced stress fiber formation in all cell lines. This was paralleled by gap formation and barrier breakdown in microvascular mesenteric endothelial cells (MesEnd), human dermal microvascular endothelial cells (HDMEC) as well as in macrovascular pulmonary artery endothelial cells (PAEC) but not in microvascular myocardial endothelial cells (MyEnd). In MyEnd cells, activation of Rac 1 and Cdc42 by CNF-1 strengthened barrier properties whereas in MesEnd, HDMEC and PAEC all three GTPases were activated which increased permeability in PAEC but not in MesEnd and HDMEC. In PAEC, CNF-1-induced decrease of barrier properties was blocked by the Rho kinase inhibitor Y27632 indicating that co-activation of Rho A dominated the barrier response. Inactivation of Rac 1 by toxin B or by lethal toxin (LT) compromised barrier properties in all cell lines. Taken together, Rac 1 requirement for endothelial barrier maintenance but not the destabilizing role of Rho A seems to be ubiquitous.

Original languageEnglish (US)
Pages (from-to)179-191
Number of pages13
JournalHistochemistry and Cell Biology
Issue number2
StatePublished - Feb 2008


  • Permeability
  • Rho proteins
  • VE-cadherin

ASJC Scopus subject areas

  • Cell Biology
  • Instrumentation


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