Advanced glycation end products increase retinal vascular endothelial growth factor expression
Advanced glycation end products increase retinal vascular endothelial growth factor expression
复制标题
DOI：
10.1172/jci1277
复制
发表时间：
1998-03-15
影响因子：
15.9
通讯作者：
Adamis, AP
中科院分区：
文献类型：
--
作者：
Lu, M;Kuroki, M;Adamis, AP
晚期糖基化终产物（AGEs）与糖尿病视网膜病变的发生有关，但其致病机制尚不清楚。缺血性和非缺血性糖尿病视网膜中血管内皮生长因子（VEGF）水平升高，并且视网膜和虹膜新血管形成需要VEGF。此外，单独的VEGF可以诱导糖尿病视网膜病变的许多伴随病理。在这项研究中，我们发现，AGEs增加血管内皮生长因子mRNA水平的神经节，内核，视网膜色素上皮（RPE）细胞层的大鼠视网膜。在体外实验中，AGEs可增加人RPE和牛血管平滑肌细胞VEGF mRNA和蛋白的分泌，AGEs诱导的VEGF表达的增加呈剂量和时间依赖性，并可被抗氧化剂抑制，且与缺氧有关。AGEs可能通过其增加视网膜VEGF基因表达的能力参与糖尿病视网膜病变的发病机制。
Advanced glycation end products (AGEs) are linked with the development of diabetic retinopathy; however, the pathogenic mechanisms are poorly defined. Vascular endothelial growth factor (VEGF) levels are increased in ischemic and nonischemic diabetic retina, and VEGF is required for the development of retinal and iris neovascularization. Moreover, VEGF alone can induce much of the concomitant pathology of diabetic retinopathy. In this study, we found that AGEs increased VEGF mRNA levels in the ganglion, inner nuclear, and retinal pigment epithelial (RPE) cell layers of the rat retina. In vitro, AGEs increased VEGF mRNA and secreted protein in human RPE and bovine vascular smooth muscle cells, The AGE-induced increases in VEGF expression were dose-and time-dependent, inhibited by antioxidants, and additive with hypoxia, Use of an anti-VEGF antibody blocked the capillary endothelial cell proliferation induced by the conditioned media of AGE-treated cells. AGEs may participate in the pathogenesis of diabetic retinopathy through their ability to increase retinal VEGF gene expression.