Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul 34450, Turkey.
Department of Physiology, School of Medicine, Koc University, Istanbul 34450, Turkey.
Int J Mol Sci. 2024 Jan 24;25(3):1403. doi: 10.3390/ijms25031403.
Pseudoexfoliation syndrome (PEX) is characterized by the accumulation of abnormal extracellular matrix material in ocular and non-ocular tissues, including blood vessel walls. Clot-forming dysfunction might be responsible for venous thrombosis in PEX. We investigated global coagulation, the proteome, and functions of platelets in PEX patients and aimed to determine prognostic biomarkers for thrombosis risk in PEX. Peripheral blood was collected from PEX and retinal vein occlusion (RVO) patients, and age-sex matched controls. Viscoelastic hemostasis was evaluated by rotational thromboelastometry (ROTEM). Platelet markers (CD41, CD42, CD61, and CD62p) and endothelial markers (P-selectin, E-selectin, and von Willebrand factor) were investigated by flow cytometry and ELISA, respectively. The platelet proteome was analyzed by 2D fluorescence difference gel electrophoresis followed by mass spectrometry. Clot formation time (CFT) is significantly reduced in PEX patients compared to the controls ( < 0.05). P-selectin levels were higher in PEX patients than in controls ( < 0.05); E-selectin and von Willebrand factor remained unchanged. The monitorization of CFT by ROTEM, and soluble P-selectin, may help assess thrombotic risk in PEX patients. Proteomic analysis revealed differential expression of Profilin-1 in platelets. Profilin-1 regulates the stability of actin-cytoskeleton and may contribute to impaired platelet hemostatic functions. Increased P-selectin levels together with impaired coagulation dynamics might be responsible for the thrombotic events in PEX disease.
假性剥脱综合征 (PEX) 的特征是异常细胞外基质物质在眼部和非眼部组织（包括血管壁）中的积累。血栓形成功能障碍可能是 PEX 患者静脉血栓形成的原因。我们研究了 PEX 患者和视网膜静脉阻塞 (RVO) 患者的整体凝血、蛋白质组和血小板功能，并旨在确定 PEX 血栓形成风险的预后生物标志物。从 PEX 和 RVO 患者以及年龄和性别匹配的对照中采集外周血。通过旋转血栓弹性测定法 (ROTEM) 评估粘弹性止血。通过流式细胞术和 ELISA 分别研究血小板标志物（CD41、CD42、CD61 和 CD62p）和内皮标志物（P 选择素、E 选择素和血管性血友病因子）。通过二维荧光差异凝胶电泳结合质谱分析血小板蛋白质组。与对照组相比，PEX 患者的血栓形成时间 (CFT) 显著缩短（<0.05）。PEX 患者的 P 选择素水平高于对照组（<0.05）；E 选择素和血管性血友病因子保持不变。通过 ROTEM 监测 CFT 和可溶性 P 选择素可能有助于评估 PEX 患者的血栓形成风险。蛋白质组分析显示 Profilin-1 在血小板中的表达存在差异。Profilin-1 调节肌动蛋白细胞骨架的稳定性，可能导致血小板止血功能受损。P 选择素水平升高和凝血动力学受损可能是 PEX 疾病中血栓事件的原因。
