Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells
Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells
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DOI：
10.1152/ajpheart.1997.273.5.h2224
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发表时间：
1997-11-01
影响因子：
4.8
通讯作者：
Nadler, J
中科院分区：
文献类型：
--
作者：
Natarajan, R;Bai, W;Nadler, J
血管内皮生长因子（VEGF）除了对内皮细胞有促进生长的作用外，还可以增加血管通透性和单核细胞迁移。因此，它与糖尿病视网膜病变和动脉粥样硬化相关的致病性新血管形成有关。然而，调节血管壁中 VEGF 表达的因素尚不完全清楚。在这项研究中，我们检查了高血糖和血管紧张素 II (ANG II) 对血管平滑肌细胞 (VSMC) 中 VEGF 表达的调节。我们还检查了 12-脂氧合酶 (12-LO) 产物 12-羟基二十碳四烯酸 (12-HETE) 是否可以改变 VEGF 表达，因为花生四烯酸的 12-LO 产物具有血管生成特性，而 ANG II 以及高葡萄糖 (HG，25 mM) 可以增加 VSMC 中的 12-LO 活性和表达。研究在人 (HSMC) 或猪 VSMC (PSMC) 中进行，这些动物在正常葡萄糖（NG，5.5 mM）或 HG 条件下培养至少两代。单独的 HG 培养物增加了 HSMC 和 PSMC 中 VEGF mRNA 和蛋白的表达。此外，ANG II 处理仅在 HG 培养的 VSMC 中显着诱导 VEGF mRNA 和蛋白表达，而在 NG 中则不显着诱导 VEGF mRNA 和蛋白表达。此外，12-HETE 显着增加了 NG 和 HG 中培养的 HSMC 中 VEGF mRNA 和蛋白的表达。在 HG 中培养的细胞也向培养基中分泌显着大量的 VEGF。这些结果表明，HG 条件下 VEGF 产量升高可能在糖尿病中观察到的加速血管疾病中发挥作用。
Vascular endothelial growth factor (VEGF), in addition to its growth-promoting effects on endothelial cells, can also increase vascular permeability and monocyte migration. It has therefore been implicated in the pathogenic neovascularization associated with diabetic retinopathy and atherosclerosis. However, the factors regulating VEGF expression in the vascular wall are not fully understood. In this study, we examined the regulation of VEGF expression in vascular smooth muscle cells (VSMC) by hyperglycemia as well as by angiotensin II (ANG II). We also examined whether the 12-lipoxygenase (12-LO) product 12-hydroxyeicosatetraenoic acid (12-HETE) can alter VEGF expression, since 12-LO products of arachidonic acid have angiogenic properties, and ANG II as well as high glucose (HG, 25 mM) can increase 12-LO activity and expression in VSMC. Studies were carried out in human (HSMC) or porcine VSMC (PSMC), which were cultured for at least two passages under normal glucose (NG, 5.5 mM) or HG conditions. HG culture alone increased the expression of VEGF mRNA and protein in both HSMC and PSMC. Furthermore, ANG II treatment significantly induced VEGF mRNA and protein expression only in VSMC cultured in HG and not NG. In addition, 12-HETE significantly increased VEGF mRNA and protein expression in HSMC cultured in NG as well as in HG. Cells cultured in HG also secreted significantly greater amounts of VEGF into the culture medium. These results suggest that elevated VEGF production under HG conditions may play a role in the accelerated vascular disease observed in diabetes.