BACKGROUND: 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. AIM OF THE STUDY: The question whether AGEs acutely induce platelet activation as a response to exogenous stimulus is addressed. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. AIM OF THE STUDY: The question whether AGEs acutely induce platelet activation as a response to exogenous stimulus is addressed. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: J Brett; A M Schmidt; S D Yan; Y S Zou; E Weidman; D Pinsky; R Nowygrod; M Neeper; C Przysiecki; A Shaw Journal: Am J Pathol Date: 1993-12 Impact factor: 4.307
Authors: Thoralf Wendt; Nozomu Tanji; Jiancheng Guo; Barry I Hudson; Angelika Bierhaus; Ravichandran Ramasamy; Bernd Arnold; Peter P Nawroth; Shi Fang Yan; Vivette D'Agati; Ann Marie Schmidt Journal: J Am Soc Nephrol Date: 2003-05 Impact factor: 10.121
Authors: Yunmei Wang; Chao Fang; Huiyun Gao; Matthew L Bilodeau; Zijie Zhang; Kevin Croce; Shijian Liu; Toshifumi Morooka; Masashi Sakuma; Kohsuke Nakajima; Shuichi Yoneda; Can Shi; David Zidar; Patrick Andre; Gillian Stephens; Roy L Silverstein; Nancy Hogg; Alvin H Schmaier; Daniel I Simon Journal: J Clin Invest Date: 2014-04-01 Impact factor: 14.808