THE EFFECT OF RHO-KINASE INHIBITION DEPENDS ON THE NATURE OF FACTORS THAT MODIFY ENDOTHELIAL PERMEABILITY
K. M. Smurova,1 A. D. Verin,2 I. B. Alieva 1, *
1 A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia,
and 2 Vascular Biology Center and Pulmonary Division, Medical College of Georgia, Augusta, USA;
* e-mail: irina_alieva@belozersky.msu.ru
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 characte-rized 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.
Key words: pulmonary endothelium, endothelial barrier function, thrombin, nocodazole, Rho-kinase, actin filaments, microtubules
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