In the human body, platelet activation occurs in response to stimuli arising from damage to the vascular wall. This initiates further reactions that help stop blood loss. Activation should not occur in normal vessels since this would lead to disturbances in blood flow inside the body. The need for a quick response in an emergency forces platelet to be in a state of “combat readiness” all the time. Platelet activation is regulated by various factors through several types of receptors.
Alexander Moskalensky, Head of the ODBSL, noted that most modern research studies the signal cascade for one factor without taking into account others. Research on the joint action of various stimuli is an important next step for understanding the mechanisms and patterns for activation of platelets in the body. Specifically, the most important inhibitory system in intact vessels is mediated by nitric oxide (NO), but it is extremely difficult to create such a system in vitro due to the fact that the NO molecule is short-lived, and in blood vessels it is constantly produced by endothelial cells.
This research project began several months ago and is designed to take place over a three year period. The researchers plan to use the accumulated experience of previous studies and to develop a method for optically releasing ligands to independently control the concentration of ADP, epinephrine, and nitric oxide (NO) in a sample. Such a multispectral system will make it possible to conduct fundamentally new experiments and not only for platelets.
Using the method developed, scientists want to obtain experimental data on the dynamics of calcium signaling in single platelets in response to the action of combined stimuli: ADP + adrenaline and ADP + NO. Moskalensky emphasized that these measurements have not been taken before anywhere in the world. There are known studies of the mutual influence of ADP and NO, but the concentration of the latter was not controlled and the calcium concentration was measured only in a suspension and not in single platelets. The system developed by NSU scientists will correct these shortcomings.
For the first time, research will be conducted on the influence of the relative timing of releasing molecules on synergism/antagonism.
Moskalensky emphasized,
This research is only possible with help from the method we developed. Already, the electronic system makes it possible to achieve a time resolution of several milliseconds, and this parameter can be improved if necessary. These measurements will make it possible to study the dynamic characteristics of platelet signaling pathways and determine parameters important for modeling. We hope that the data obtained in the future will make it possible to more rationally control the work of the platelet component of hemostasis in clinical practice and for the prevention of diseases.
