Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. Georgi Bonchev, Str. Bl. 21, 1113 Sofia, Bulgaria.
Department of Biochemistry, Medical University, 1 St. Kliment Ohridski Str., 5800 Pleven, Bulgaria.
Int J Mol Sci. 2021 Jul 21;22(15):7778. doi: 10.3390/ijms22157778.
Pregnancy is associated with hypercoagulation states and increased thrombotic risk, especially in women with thrombophilia. We combine atomic force microscopy (AFM) and flow cytometry to examine the morphology and nanomechanics of platelets derived from women with early pregnancy loss (EPL) and control pregnant (CP) and non-pregnant (CNP) women. Both control groups exhibit similar morphometric parameters (height and surface roughness) and membrane stiffness of platelets. EPL patients' platelets, on the other hand, are more activated than the control groups, with prominent cytoskeletal rearrangement. In particular, reduced membrane roughness (22.9 ± 6 nm vs. 39.1 ± 8 nm) ( < 0.05) and height (692 ± 128 nm vs. 1090 ± 131 nm) ( < 0.05), strong alteration in the membrane Young modulus, increased production of platelets' microparticles, and higher expression of procoagulant surface markers, as well as increased occurrence of thrombophilia (, , , or 4G/5G ) polymorphisms were found. We suggest that the carriage of thrombophilic mutations triggers structural and nanomechanical abnormalities in platelets, resulting in their increased activation. The activation state of platelets can be well characterized by AFM, and the morphometric and nanomechanical characteristics might serve as a new criterion for evaluation of the cause of miscarriage and offer the prospect of an innovative approach serving for diagnostic purposes.
妊娠与高凝状态和血栓形成风险增加有关，尤其是在血栓形成倾向的妇女中。我们结合原子力显微镜（AFM）和流式细胞术来研究早发性妊娠丢失（EPL）和对照孕妇（CP）及非孕妇（CNP）妇女来源的血小板的形态和纳米力学。两个对照组的血小板具有相似的形态参数（高度和表面粗糙度）和膜硬度。另一方面，EPL 患者的血小板比对照组更活跃，细胞骨架重排明显。特别是，EPL 患者的血小板膜粗糙度（22.9±6nm 对 39.1±8nm）（<0.05）和高度（692±128nm 对 1090±131nm）（<0.05）降低，膜杨氏模量明显改变，血小板微颗粒生成增加，促凝表面标志物表达增加，以及血栓形成倾向（，，，或 4G/5G）突变的发生率增加。我们认为，携带血栓形成倾向的突变会导致血小板的结构和纳米力学异常，从而导致其过度激活。AFM 可很好地描述血小板的激活状态，形态和纳米力学特征可能成为评估流产原因的新标准，并为诊断目的提供创新方法的前景。
