Abstract

In circulated blood, platelets are controlled by stimulatory and inhibitory factors and tightly regulated equilibrium between these two opposing processes is essential for normal platelet and vascular function. NO/cGMP/PKG pathway plays one of the most significant roles in platelet inhibition. However, recently in the literature appeared some new hypothesis that PKG pathway plays a stimulatory or dual role in platelets. Three main points are in the focus of our review i) stimulatory, or dual role of PKG in platelets with a particular emphasis on the pitfalls, artifacts, and incorrect interpretations of the data that leads to developing these new hypotheses, ii) data on new PKG substrates in platelets which are involved in different mechanisms of PKG-mediated platelet inhibition, and iii) clinical aspects of NO-liberating drugs and sGC activation. In conclusions, we suggested that recently developed quantitative phosphoproteomic method might be one of the most powerful tools for analysis of PKG-mediated effects. Analysis of phosphoproteins in PKG activated platelets will reveal many new PKG substrates. Future validations of these substrates and their involvement on different platelet inhibitory pathways could be a basis for the development of new antiplatelet drugs that might target only specific aspects of platelet functions.

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