The effect of rho-kinase inhibition depends on the nature of factors that modify endothelial permeability

K. M. Smurova, Alexander Dmitriyevich Verin, I. B. Alieva

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Endothelium lining the inner surface of all vessels plays barrier role and regulates permeability of vascular walls controling the exchange between circulating blood and tissue fluids. Disturbance of normal functions (endothelial dysfunction) can be caused by both internal, and external factors. Endothelial dysfunction is characterized by increased vascular wall permeability observed in many human diseases. Dysfunction is also a drug side effect of oncological diseases treatment by mitosis-blocking medications. Depolymerization of microtubules is the first step in the cascade of reactions leading to endothelial barrier dysfunction, and this stage is universal, it does not depend upon the nature of a factor provoking dysfunction. To develop the strategy of barrier dysfunction prevention, we are supposed here to find out to what stage the endothelial cell cytoskeleton reaction during the development of barrier dysfunction is universal. It has been found that the cascade stages, which follow the microtubule depolymerization and are connected with Rho-Rho-kinases activity, have the features depending on the factor provoking barrier dysfunction. Under suppression of Rho-kinase activity, the reaction of actin filaments does not depend on what substance caused dysfunction. But the microtubule system responds to the treatment varies depending on the dysfunction-provoking factor. Unlike thrombin, under the conditions of Rho-kinase activity suppression, nocodazole renders more strong effect, as much as possible destroying both dynamic, and stable microtubules. Thus, regardless of the dysfunction provoking factor, the initial stages of dysfunction connected with the depolymerization of microtubules appear to be unalterable. Consequently, endothelial cell defence strategy should be based on cytoplasmatic microtubules protectors application instead of employment of the factors involved in the cascade at later stages as we assumed earlier.

Original languageEnglish (US)
Pages (from-to)359-366
Number of pages8
JournalTsitologiya
Volume53
Issue number4
StatePublished - Aug 8 2011

Keywords

  • Actin filaments
  • Endothelial barrier function
  • Microtubules
  • Nocodazole
  • Pulmonary endothelium
  • Rho-kinase
  • Thrombin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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