Angiotensin II upregulates the expression of placental growth factor in human vascular endothelial cells and smooth muscle cells.
Angiotensin II upregulates the expression of placental growth factor in human vascular endothelial cells and smooth muscle cells.
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血管紧张素 II 上调人血管内皮细胞和平滑肌细胞中胎盘生长因子的表达。
DOI：
10.1186/1471-2121-11-36
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发表时间：
2010-05-26
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Pan P;Fu H;Zhang L;Huang H;Luo F;Wu W;Guo Y;Liu X
研究背景动脉粥样硬化是一种慢性炎症性疾病。血管紧张素II（Angiotensin II，Ang II）是炎症反应中的重要因子，促进动脉粥样硬化的发生发展。胎盘生长因子（PlGF）是血管内皮生长因子（VEGF）家族细胞因子的一员，与动脉粥样硬化的炎症进展相关。然而，尚未研究PlGF和Ang II之间的潜在联系。本研究以人血管内皮细胞（VECs）和平滑肌细胞（VSMCs）为研究对象，探讨了血管紧张素Ⅱ（Ang Ⅱ）对PlGF表达的调控作用，以及PlGF对VECs和VSMCs增殖的影响。10- 6 mol/LAngII处理8h后PlGF蛋白表达增加，24 h达高峰。血管紧张素II刺激也诱导VEGF受体-1和-2（VEGFR-1和-2）在这些细胞中的mRNA表达。血管紧张素Ⅱ I型受体（AT 1 R）拮抗剂阻断血管紧张素Ⅱ诱导的PlGF基因表达和蛋白质产生。Ang Ⅱ引起的多种细胞内信号参与了PlGF的合成，包括蛋白激酶C、细胞外信号调节激酶1/2（ERK 1/2）和PI 3-激酶的激活。抗PlGF中和抗体可部分抑制Ang Ⅱ诱导的VECs和VSMCs增殖。然而，这种抗体显示在这些细胞的基础增殖的影响不大，而VEGF的阻断抗体可以抑制基础和Ang II诱导的增殖VECs和VSMCs.ConclusionOur结果表明，第一次，Ang II可以诱导VECs和VSMCs的基因表达和蛋白质的产生，这可能在血管炎症和动脉粥样硬化的发病机制中发挥重要作用。
BackgroundAtherosclerosis is now recognized as a chronic inflammatory disease. Angiotensin II (Ang II) is a critical factor in inflammatory responses, which promotes the pathogenesis of atherosclerosis. Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family cytokines and is associated with inflammatory progress of atherosclerosis. However, the potential link between PlGF and Ang II has not been investigated. In the current study, whether Ang II could regulate PlGF expression, and the effect of PlGF on cell proliferation, was investigated in human vascular endothelial cells (VECs) and smooth muscle cells (VSMCs).ResultsIn growth-arrested human VECs and VSMCs, Ang II induced PlGF mRNA expression after 4 hour treatment, and peaked at 24 hours. 10-6mol/L Ang II increased PlGF protein production after 8 hour treatment, and peaked at 24 hours. Stimulation with Ang II also induced mRNA expression of VEGF receptor-1 and -2(VEGFR-1 and -2) in these cells. The Ang II type I receptor (AT1R) antagonist blocked Ang II-induced PlGF gene expression and protein production. Several intracellular signals elicited by Ang II were involved in PlGF synthesis, including activation of protein kinase C, extracellular signal-regulated kinase 1/2 (ERK1/2) and PI3-kinase. A neutralizing antibody against PlGF partially inhibited the Ang II-induced proliferation of VECs and VSMCs. However, this antibody showed little effect on the basal proliferation in these cells, whereas blocking antibody of VEGF could suppress both basal and Ang II-induced proliferation in VECs and VSMCs.ConclusionOur results showed for the first time that Ang II could induce the gene expression and protein production of PlGF in VECs and VSMCs, which might play an important role in the pathogenesis of vascular inflammation and atherosclerosis.
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影响因子：
7.4
作者：
Martín de Llano JJ;Fuertes G;Torró I;García Vicent C;Fayos JL;Lurbe E
通讯作者：
Lurbe E
影响因子：
37.8
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影响因子：
24
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通讯作者：
Boersma, E
影响因子：
4.8
作者：
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通讯作者：
De Falco, S