VEGF-A induces expression of eNOS and iNOS in endothelial cells via VEGF receptor-2 (KDR)
VEGF-A induces expression of eNOS and iNOS in endothelial cells via VEGF receptor-2 (KDR)
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DOI：
10.1006/bbrc.1998.9719
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发表时间：
1998-11-27
影响因子：
3.1
通讯作者：
Waltenberger, J
中科院分区：
文献类型：
--
作者：
Kroll, J;Waltenberger, J
血管内皮生长因子-A (VEGF-A) 是一种内皮特异性生长因子，可诱导血管生成，即体内已有血管中毛细血管的萌芽。内皮一氧化氮合酶 (eNOS) 是通过产生一氧化氮 (NO) 介导 VEGF-A 诱导的血管生成和内皮功能的重要分子。此外，eNOS 的蛋白水平响应 VEGF-A 而上调。虽然人滋养层细胞中 VEGF-A 诱导的 NO 释放似乎是通过 VEGF 受体 1 启动的，但尚不清楚哪种 VEGF 受体介导诱导 eNOS 蛋白表达的信号。此外，尚不清楚其他 NOS 亚型是否会因 VEGF-A 刺激而上调。为了解决这些问题，我们用 VEGF-A 刺激人脐静脉内皮细胞 (HUVEC) 24 小时，并评估 eNOS 和 iNOS 蛋白的表达。 VEGF-A 诱导 NOS 家族两个成员的表达。利用过表达 VEGF 受体-a（PAE/KDR 细胞）或 VEGF 受体-1（PAE/Flt-1 细胞）的猪主动脉内皮细胞，我们研究了 VEGF-A 刺激对 iNOS 和 eNOS 表达的调节。 VEGF受体2的激活导致eNOS和iNOS蛋白的上调，而VEGF受体1的刺激不会产生这样的信号，因此，只有VEGF受体2介导eNOS和iNOS表达的刺激，我们得出结论，这两种VEGF受体在VEGF-A诱导的血管生成过程中对于NO形成和NO释放具有不同且不同的功能。 (C) 1998 年学术出版社。
Vascular Endothelial Growth Factor-A (VEGF-A) is an endothelial-specific growth factor that induces angiogenesis, i.e., sprouting of capillaries from preexisting vessels in vivo. Endothelial nitric oxide synthase (eNOS) is an essential molecule in mediating VEGF-A-induced angiogenesis and endothelial function via production of nitric oxide (NO). Moreover, the protein level of eNOS is upregulated in response to VEGF-A. While VEGF-A-induced NO release in human trophoblast cells appears to be initiated via VEGF receptor-1, it is not clear which of the VEGF-receptors is mediating the signal for induction of eNOS protein expression. In addition, it is unclear whether other NOS isoforms are upregulated in response to VEGF-A stimulation, To address these questions, we stimulated human umbilical vein endothelial cells (HUVEC) with VEGF-A for 24 hours and evaluated expression of eNOS and iNOS protein. VEGF-A induces expression of both members of the NOS family, Using porcine aortic endothelial cells overexpressing either VEGF receptor-a (PAE/KDR cells) or VEGF receptor-1 (PAE/Flt-1 cells), we have studied the regulation of iNOS and eNOS expression in response to VEGF-A stimulation. The activation of VEGF receptor-2 leads to an upregulation of both eNOS and iNOS protein, while stimulation of VEGF receptor-1 did not generate such a signal, Therefore, only VEGF receptor-2 mediates stimulation of eNOS and iNOS expression, We conclude that the two VEGF receptors have different and distinct functions regarding NO formation and NO release during VEGF-A-induced angiogenesis. (C) 1998 Academic Press.