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Effect of advanced glycation end products on platelet activation and aggregation: a comparative study of the role of glyoxal and methylglyoxal

机译:晚期糖化末端产物对血小板激活和聚集的影响:乙醛和甲基乙醛作用的对比研究

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Advanced glycation end products (AGEs) arising from dietary intake have been associated with numerous chronic diseases including cardiovascular diseases. The interaction between platelets and AGEs has been proposed to play a role in the etiology of cardiovascular diseases. However, the effects of the interaction between platelets and Maillard reaction products generated from glyoxal (Gly) or methylglyoxal (MG) are poorly understood. In this work, the effects of AGEs generated by the reaction between Gly or MG with Lys or bovine serum albumin (BSA) on platelet activation and aggregation were assessed. AGEs were generated incubating Gly or MG with Lys or BSA during 5 hours or 14 days, respectively. AGEs generation were characterized by kinetic studies and by amino acid analysis. Human platelet-rich plasma (PRP) was incubated with different concentrations of AGEs from Lys-MG or Lys-Gly and BSA-MG or BSA-Gly. Platelet activation was determined quantifying the expression of CD62 (P-selectin) in PRP exposed to different AGEs concentrations. It was found that Lys-MG and Lys-Gly induced an increase in P-selectin expression (p < .05), being 33.9% higher for Lys-MG when compared to Lys-Gly. Platelets incubated in the presence of BSA-MG and BSA-Gly did not show an increase in the P-selectin expression. Platelet aggregation was significantly higher for the mixture Lys-MG (in all the range of concentrations evaluated), whereas for Lys-Gly it was only significant the highest concentration (Lys 168 mu M/Gly 168 mu M). It was observed a significant increase in platelet aggregation induced by ADP for samples BSA-Gly. AGEs formed with MG-Lys induce a higher activation and aggregation of platelets when compared to those formed from Gly-Lys.
机译:饮食摄入引起的晚期糖基化终产物(AGEs)与包括心血管疾病在内的许多慢性疾病有关。血小板和AGEs之间的相互作用被认为在心血管疾病的病因中起作用。然而,血小板与乙二醛(Gly)或甲基乙二醛(MG)产生的美拉德反应产物之间的相互作用的影响尚不清楚。本研究评估了甘氨酸或镁与赖氨酸或牛血清白蛋白(BSA)反应产生的AGE对血小板活化和聚集的影响。将甘氨酸或镁与赖氨酸或BSA分别在5小时或14天内孵育产生AGE。AGEs的产生通过动力学研究和氨基酸分析进行表征。人富血小板血浆(PRP)与来自Lys-MG或Lys-Gly和BSA-MG或BSA-Gly的不同浓度AGEs一起孵育。通过量化不同AGEs浓度下PRP中CD62(P-选择素)的表达来测定血小板活化。发现Lys-MG和Lys-Gly诱导P-选择素表达增加(P<0.05),与Lys-Gly相比,Lys-MG的P-选择素表达增加33.9%。在BSA-MG和BSA-Gly存在下培养的血小板没有显示P-选择素表达的增加。混合物Lys-MG(在所有评估的浓度范围内)的血小板聚集显著更高,而Lys-Gly仅在最高浓度(Lys 168μM/Gly 168μM)时显著。在样品BSA-Gly中观察到ADP诱导的血小板聚集显著增加。与甘氨酸-赖氨酸形成的AGEs相比,用MG-Lys形成的AGEs诱导血小板的更高活化和聚集。

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