Szelenberger Rafał, Karbownik Michał Seweryn, Kacprzak Michał, Synowiec Ewelina, Michlewska Sylwia, Bijak Michał, Zielińska Marzenna, Olender Alina, Saluk-Bijak Joanna
Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
Biohazard Prevention Centre, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
Biology (Basel). 2022 Apr 22;11(5):644. doi: 10.3390/biology11050644.
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.
血小板活化所引起的病理状况是急性冠脉综合征(ACS)发病机制的核心基础。ACS中血小板的过度活跃已有充分记录,但对于血小板功能表型变化的分子基础仍研究甚少。为了拓展对这一现象的认识,我们分析了几种关键血小板受体表达的紊乱情况以及调节潜在异常的方面。血小板表面受体负责维持止血平衡、血小板与免疫细胞的相互作用以及支持导致血管腔阻塞的凝血级联反应。由于其突出作用,血小板受体构成了药物治疗的主要靶点。我们的研究旨在确定血小板表面受体的分子改变,结果显示ACS中P2Y12、GP1BB、ITGA2B和ITGB3的mRNA表达增加,以及P2Y12和GP IIb/IIIa的蛋白浓度升高。共聚焦和细胞计数可视化也证实了P2Y12水平的上调。此外,我们评估了两种微小RNA:miR-223-3p和miR-126-3p的表达,它们被认为可调节血小板P2Y12的表达。我们的研究结果为ACS的分子背景提供了新的见解。