Dysregulation in the Expression of Platelet Surface Receptors in Acute Coronary Syndrome Patients-Emphasis on P2Y12

Simple Summary Acute Coronary Syndrome is a disease of the circulatory system characterized by the partial or complete blockage of coronary arteries. In thrombosis, a major role is played by platelets-the smallest, anucleate, morphotic elements in the bloodstream. Platelets are involved in the process of hemostasis, which ensures the continuity of the blood vessel by forming a clot that prevents blood loss. Unique structures of blood platelets ensure their high reactivity in the vascular microenvironment due to the interaction with many biologically active molecules, which is recognized by the surface receptors. The research carried out in the manuscript is aimed at detecting potential changes at the molecular level in platelet surface receptors that could constitute the potential importance of the occurrence of Acute Coronary Syndrome. The obtained results indicate that the P2Y12 receptor, which is the main target of antiplatelet therapy, is expressed more frequently among patients. In addition, we have shown that at the genetic level, quantitative changes also occur in the case of other receptors that are important in the activation of platelets. The following manuscript suggests the potential mechanisms responsible for the differences between patients and healthy donors due to a better understanding of the molecular causes of Acute Coronary Syndrome pathogenesis. The pathological conditions caused by blood platelet activation constitute a fundamental core in the pathogenesis of Acute Coronary Syndrome (ACS). The hyperactivity of platelets in ACS is well-documented, but there is still little research into the molecular basis of phenotypic changes in platelet functionality. To expand the knowledge of this phenomenon, we analyzed the disturbances in the expression of several key platelet receptors and the aspect of regulating potential abnormalities. Platelet surface receptors are responsible for maintaining the hemostatic balance, platelet interaction with immune cells, and support of the coagulation cascade leading to occlusion of the vessel lumen. Due to their prominent role, platelet receptors constitute a major target in pharmacological treatment. Our work aimed to identify the molecular alteration of platelet surface receptors, which showed augmented mRNA expression of P2Y12, GP1BB, ITGA2B, and ITGB3 and increased protein concentrations of P2Y12 and GP IIb/IIIa in ACS. The upregulation of the P2Y12 level was also confirmed by confocal and cytometric visualization. Furthermore, we evaluated the expression of two microRNAs: miR-223-3p and miR-126-3p, which were suggested to regulate platelet P2Y12 expression. Results of our study present new insight into the molecular background of ACS.

Automated summary

This study aims to detect potential changes at the molecular level in platelet surface receptors that could be of potential importance in the occurrence of Acute Coronary Syndrome. The results show that the P2Y12 receptor is expressed more frequently among patients, and there are quantitative changes in other platelet receptors important in platelet activation at the genetic level.