Heart and Diabetes Center NRW, Ruhr-University Bochum, Georgstrasse 11, 32545, Bad Oeynhausen, Germany.
Eur J Nutr. 2009 Dec;48(8):475-81. doi: 10.1007/s00394-009-0038-6. Epub 2009 Jul 26.
Diabetes mellitus is characterized by hyperglycemia that plays an important role in the pathogenesis of diabetic complications including cardiovascular diseases. Moreover, hyperglycemia induces increased generation of advanced glycation end products (AGEs). The activation of platelets is associated with the development of cardiovascular diseases.
The question whether AGEs acutely induce platelet activation as a response to exogenous stimulus is addressed.
The effect of AGEs derived from food and human serum being purified by lysozyme affinity chromatography was examined by incubating in vitro freshly isolated blood platelets from fasted subjects at various concentrations and different time points. Platelet activation, determined as expression of surface markers CD62 and CD63, and the presence of the receptor for AGEs (RAGE) in platelet membranes was measured by flow cytometric analysis using specific antibodies.
Incubation with food-derived as well as serum-derived AGEs stimulated significantly the expression of CD62 up to 7.1-fold and CD63 up to 2.2-fold at the platelet surface membrane as a function of concentration and time. Incubation with thrombin or AGEs significantly increased RAGE expression twofold at the platelet surface membrane.
The increase in surface activation marker and RAGE expression in platelets, resulting from concentrations of AGEs that occur in vivo after a meal or a drink as a source of exogenous AGEs, points to signaling mechanisms for food AGEs that could favor the precipitation of acute postprandial ischemic events.
糖尿病的特征是高血糖，它在包括心血管疾病在内的糖尿病并发症的发病机制中起着重要作用。此外，高血糖会导致晚期糖基化终产物（AGEs）的生成增加。血小板的激活与心血管疾病的发展有关。
本研究旨在探讨 AGEs 是否会作为对外源刺激的反应而急性诱导血小板激活。
通过用溶菌酶亲和层析法从食物和人血清中纯化 AGEs，在不同浓度和不同时间点体外孵育空腹受试者的新鲜分离血小板，来检测 AGEs 的作用。通过使用特异性抗体的流式细胞术分析，测定血小板表面标志物 CD62 和 CD63 的表达以及血小板膜上 AGEs 受体（RAGE）的存在，来评估血小板的激活情况。
与食物来源的 AGEs 或血清来源的 AGEs 孵育均可显著刺激 CD62 表达，在血小板表面膜上最高可达 7.1 倍，CD63 表达最高可达 2.2 倍，其作用呈浓度和时间依赖性。与凝血酶或 AGEs 孵育可使血小板表面膜上的 RAGE 表达增加两倍。
由于饮食或饮料作为外源性 AGEs 的来源，体内摄入 AGEs 后会导致血小板表面活化标志物和 RAGE 表达增加，这表明了食物 AGEs 的信号转导机制可能有利于急性餐后缺血事件的发生。
