Differential modulation of angiogenesis by advanced glycation end products
Differential modulation of angiogenesis by advanced glycation end products
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DOI：
10.1258/ebm.2010.010087
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发表时间：
2011-01-01
影响因子：
3.2
通讯作者：
Sudhakaran, Perumana R.
中科院分区：
文献类型：
--
作者：
Devi, Manju S.;Sudhakaran, Perumana R.
不同的血管生成反应发生在不同的器官在糖尿病状态。许多病理效应是由非酶糖化分子的晚期糖化终产物（AGEs）介导的。使用不同的血管生成模型系统进行调查，以检查血管生成反应AGEs是否受到细胞微环境的影响。AGE-白蛋白可促进鸡胚绒毛尿囊膜（CAM）血管生成。它还增加了大鼠主动脉环中的发芽以及培养的人脐静脉内皮细胞（HUVECs）中的血管生成标记物CD 31和E-选择素以及血管生成生长因子、血管内皮生长因子（VEGF）的表达，表明了促血管生成作用。但在血清补充条件下，AGE-白蛋白抑制主动脉发芽和血管生成标记物的表达和血管内皮细胞的VEGF的生产，表明血清存在下的抗血管生成作用。抗氧化剂N-乙酰半胱氨酸和抗坏血酸阻断AGE效应，表明AGE效应涉及氧化应激。LY 294 002（Akt通路的抑制剂）对AGE效应的抑制作用以及在无血清培养基中维持的细胞中Akt磷酸化的增加，表明Akt通路参与介导AGE效应;在补充血清的条件下不存在这种效应。在血清存在和不存在的情况下，AGE-白蛋白对血管生成的这些相反的作用表明，在高血糖条件下积累的AGE可以影响血管生成，这取决于细胞的微环境。
Divergent angiogenic responses occur in different organs in a diabetic state. Many of the pathological effects were mediated by the advanced glycation end products (AGEs) of non-enzymatically glycated molecules. Investigations were carried out using different angiogenic model systems to examine whether the angiogenic response to AGEs is influenced by the cellular microenvironment. AGE-albumin increased angiogenesis in chick chorioallantoic membrane (CAM). It also increased sprouting in rat aortic rings and the expression of angiogenic markers CD31 and E-selectin and the angiogenic growth factor, vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs) in culture, suggesting a proangiogenic effect. But in a serum-supplemented condition, AGE-albumin inhibited aortic sprouting and expression of angiogenic markers and VEGF production by HUVECs, suggesting an antiangiogenic effect in the presence of serum. Blocking of the AGE effect by the antioxidants, N-acetyl cysteine and ascorbic acid, suggested that the AGE effect involved oxidant stress. Reversal of the AGE effect by LY 294 002, an inhibitor of the Akt pathway and increased phosphorylation of Akt in cells maintained in serum-free medium, suggested the involvement of the Akt pathway in mediating the AGE effect; such an effect was absent in a serum-supplemented condition. These opposing effects of AGE-albumin on angiogenesis in the presence and absence of serum suggested that the AGE accumulated in a hyperglycemic condition can affect angiogenesis depending on the microenvironment of the cells.