ACE2 Antagonizes VEGFa to Reduce Vascular Permeability During Acute Lung Injury
ACE2 Antagonizes VEGFa to Reduce Vascular Permeability During Acute Lung Injury
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DOI：
10.1159/000443056
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发表时间：
2016-03
影响因子：
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通讯作者：
Xiaobo Yu;Q. Lin;X. Qin;Z. Ruan;Jianhua Zhou;Zhi-feng Lin;Yijiang Su;Jian Zheng;Zhenwei Liu-Zhenwe
中科院分区：
文献类型：
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作者：
Xiaobo Yu;Q. Lin;X. Qin;Z. Ruan;Jianhua Zhou;Zhi-feng Lin;Yijiang Su;Jian Zheng;Zhenwei Liu-Zhenwe
背景/目标：血管紧张素转换酶2（ACE 2）通过拮抗血管紧张素II（AngII）的水解和肺内皮细胞的凋亡而减轻急性肺损伤（ALI）的严重程度。然而，ACE 2对血管通透性的影响及其与血管内皮生长因子a（VEGFa）的关系仍然不明确。在本研究中，我们检测了小鼠ALI模型中ACE 2和VEGFa之间的关系。方法：采用博莱霉素诱导小鼠急性肺损伤模型，并给予ACE 2治疗。我们分析了这些小鼠中的VEGFa水平。静脉注射62.5µg/kg Visudyne后，通过荧光药代动力学试验测定小鼠肺血管通透性。分别给予VEGFa泵或SU 5416泵以增强或减弱VEGFa效应。通过使用乙酰甲胆碱测量肺阻力来确定对肺功能的长期影响。结果：ACE 2处理不改变肺组织VEGFa水平，但能拮抗VEGFa对肺血管通透性增加的作用。外源性VEGFa可阻断ACE 2对血管通透性的拮抗作用。另一方面，VEGF信号传导的抑制模拟了ACE 2对血管对VEGFa的渗透性的作用。肺血管通透性降低可改善ALI后肺功能。结论：ACE 2可拮抗VEGF α介导的肺血管通透性增加，从而改善ALI后肺功能。
Background/Aims: Angiotensin converting enzyme 2 (ACE2) treatment suppresses the severity of acute lung injury (ALI), through antagonizing hydrolyzing angiotensin II (AngII) and the ALI-induced apoptosis of pulmonary endothelial cells. Nevertheless, the effects of ACE2 on vessel permeability and its relationship with vascular endothelial growth factor a (VEGFa) remain ill-defined. In the current study, we examined the relationship between ACE2 and VEGFa in ALI model in mice. Methods: Here, we used a previously published bleomycin method to induce ALI in mice, and treated the mice with ACE2. We analyzed the levels of VEGFa in these mice. The mouse lung vessel permeability was determined by a fluorescence pharmacokinetic assay following i.v. injection of 62.5µg/kg Visudyne. VEGFa pump or SU5416 pump was given to increase or decrease VEGFa effects, respectively. The long-term effects on lung function were determined by measurement of lung resistance using methacholine. Results: ACE2 treatment did not alter VEGFa levels in lung, but antagonized the effects of VEGFa on increases of lung vessel permeability. Ectogenic VEGFa abolished the antagonizing effects of ACE2 on the vessel permeability against VEGFa. On the other hand, suppression of VEGF signaling mimicked the effects of ACE2 on the vessel permeability against VEGFa. The suppression of vessel permeability resulted in improvement of lung function after ALI. Conclusion: ACE2 may antagonize the VEGFa-mediated increases in lung vessel permeability during ALI, resulting in improvement of lung function after ALI.