甲基乙二醛
糖基化
外周血单个核细胞
血小板
化学
血小板活化
流式细胞术
细胞凋亡
P-选择素
细胞粘附分子
免疫学
发病机制
药理学
男科
内科学
内分泌学
糖尿病
医学
生物化学
体外
酶
作者
Thomas Gawlowski,Bernd Stratmann,Alin Stirban,Monica Negrean,Diethelm Tschöepe
标识
DOI:10.1016/j.thromres.2007.03.002
摘要
Diabetes mellitus is characterised by hyperglycaemia that plays an important role in the pathogenesis of diabetic complications including accumulation of methylglyoxal (MG), a highly reactive alpha-dicarbonyl metabolite of glucose degradation pathways and increased generation of advanced glycation end products (AGEs). The aim of this study was to investigate the impact of AGE-BSA, the model substance for AGEs, and MG on cellular haemostasis.Isolated peripheral blood mononuclear cells (PBMCs) or whole blood was incubated with AGE-BSA and MG. Markers of cellular haemostasis were monitored by flow cytometry.Exposure of PBMCs to AGE-BSA and MG resulted in a dose- and time-dependent increase of TF-expression by monocytes. AGE-BSA and MG induced enhanced platelet-neutrophil aggregation. Examination of platelet activation showed that AGE-BSA induces no direct effect on the expression of P-selectin. However, stimulation with MG resulted in a dose-dependent expression of P-selectin by platelets. Stimulation with AGE-BSA or MG markedly increased dose-dependent expression of Apo2.7 on the neutrophil mitochondria. In addition the analysis demonstrated for the first time that both AGE-BSA and MG induce a dose-dependent expression of the adhesion molecule Mac-1 on the surface of neutrophils.AGE-BSA as well as MG induced apoptosis of neutrophils and enhanced expression of the adhesion molecule Mac-1 resulting in increased formation of platelet-neutrophil aggregates. These findings may contribute to better understand the mechanism of diabetic thrombosis and the associated high cardiovascular risk of diabetic patients.
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