Expression and secretion of neuregulin-1 in cardiac microvascular endothelial cells treated with angiogenic factors.
Expression and secretion of neuregulin-1 in cardiac microvascular endothelial cells treated with angiogenic factors.
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DOI：
10.3892/etm.2018.5811
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发表时间：
2018-04
影响因子：
2.7
通讯作者：
Chengqiang Wu;Chun Gui;Lang Li;Yiheng Pang;Zhong-li Tang;Jing Wei
中科院分区：
文献类型：
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作者：
Chengqiang Wu;Chun Gui;Lang Li;Yiheng Pang;Zhong-li Tang;Jing Wei
神经调节蛋白-1（NRG-1）是血管生成的正性调节因子，这表明NRG-1与血管生成因子之间可能存在关联。本研究的目的是研究血管生成因子对人心脏微血管内皮细胞（HCMEC）NRG-1表达和分泌的影响。在正常或缺氧/血清剥夺（Hypo/SD）条件下培养HCMEC并用血管内皮生长因子（VEGF; 100 ng/ml）、血管生成素（Ang）-1（100 ng/ml）或Ang-2（100 ng/ml）刺激24 h。通过Western印迹分析测定HCMEC中ErbB受体和NRG-1的表达，并通过ELISA测定HCMEC中NRG-1的分泌。结果表明，ErbB 2、ErbB 3和ErbB 4在HCMEC中均有表达，且ErbB 2的表达水平明显高于ErbB 3和ErbB 4。在正常培养条件下，VEGF和Ang-1处理组NRG-1的表达和分泌均明显增加（P<0.05），而Ang-2处理组NRG-1的表达和分泌明显减少（P<0.05）。Hypo/SD组NRG-1的表达和分泌显著增加（P<0.05），VEGF或Ang-1处理组NRG-1的表达和分泌进一步增加（P<0.05）。而Ang-2治疗组则显著降低上述作用（P<0.05）。VEGF和Ang-1处理组NRG-1的表达和释放均显著增加（P<0.05），提示VEGF和Ang-1可能通过NRG-1/ErbB信号通路调节心肌血管生成和存活。
Neuregulin-1 (NRG-1) is a positive regulator of angiogenesis, which suggests there may be an association between NRG-1 and angiogenic factors. The aim of the present study was to investigate the effect of treating human cardiac microvascular endothelial cells (HCMECs) with angiogenic factors on NRG-1 expression and secretion. HCMECs were cultured and stimulated with vascular endothelial growth factor (VEGF; 100 ng/ml), angiopoietin (Ang)-1 (100 ng/ml) or Ang-2 (100 ng/ml) under normal or hypoxia/serum deprivation (Hypo/SD) conditions for 24 h. The expression of ErbB receptors and NRG-1 in HCMECs was measured by western blot analysis and the secretion of NRG-1 in HCMECs was determined by ELISA. The results demonstrated that ErbB2, ErbB3 and ErbB4 were expressed in HCMECs and that ErbB2 expression levels were notably higher than those of ErbB3 and ErbB4. Under normal culture conditions the expression and secretion of NRG-1 was significantly increased in HCMECs treated with VEGF or Ang-1 (P<0.05), however levels significantly decreased in HCMECs treated with Ang-2 (P<0.05). Under Hypo/SD conditions the expression and secretion of NRG-1 significantly increased (P<0.05) and VEGF or Ang-1 treatment significantly increased these effects further (P<0.05). Conversely Ang-2 treatment significantly decreased these effects (P<0.05). The expression and release of NRG-1 were significantly increased in HCMECs with VEGF or Ang-1 treatment (P<0.05), which suggests that VEGF and Ang-1 may regulate myocardial angiogenesis and survival via the NRG-1/ErbB signaling pathway.