Hyperbaric oxygen activates visfatin expression and angiogenesis via angiotensin II and JNK pathway in hypoxic human coronary artery endothelial cells
Hyperbaric oxygen activates visfatin expression and angiogenesis via angiotensin II and JNK pathway in hypoxic human coronary artery endothelial cells
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DOI：
10.1111/jcmm.14926
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发表时间：
2020-01-19
影响因子：
5.3
通讯作者：
Shyu, Kou-Gi
中科院分区：
文献类型：
--
作者：
Chiu, Chiung-Zuan;Wang, Bao-Wei;Shyu, Kou-Gi
内脂素是一种脂肪细胞因子，在内皮血管生成中具有重要作用。高压氧（HBO）已被广泛用于治疗各种具有增强血管生成的医学疾病。低氧条件下HBO对内脂素的分子效应尚不清楚。本研究旨在探讨高压氧对缺氧人冠状动脉内皮细胞内脂素的影响。将化学缺氧（抗霉素A，0.01mmol/L）下的HCAEC暴露于HBO（2.5大气压绝对压力; ATA）2-4小时。Western印迹，实时聚合酶链反应，电泳迁移率变动分析，荧光素酶启动子活性，迁移和管形成分析，并在体外葡萄糖摄取进行了测定。内脂素蛋白表达在缺氧HCAECs中增加，早期血管紧张素II（AngII）分泌和c-Jun N-末端激酶（JNK）磷酸化，这可以被JNK抑制剂（SP 600125）、AngII抗体或AngII受体阻断剂（losartan）有效地抑制。在缺氧HCAEC中，HBO进一步诱导visfatin和AngII的早期表达。缺氧显著增加缺氧诱导因子-1 α（HIF-1 α）和内脂素的DNA-蛋白结合活性。缺氧，缺氧与HBO和外源性添加AngII也增加了启动子内脂素的转录，SP 600125和氯沙坦阻断这种活动。在HCAECs中，葡萄糖摄取，迁移和管形成在缺氧和HBO的存在下增加，但visfatin小干扰RNA，SP 600125和氯沙坦抑制。总之，HBO激活内脂素的表达和缺氧HCAECs血管生成，AngII介导的效果，主要通过JNK通路。
Visfatin is an adipocytokine with important roles in endothelial angiogenesis. Hyperbaric oxygen (HBO) has been widely used to treat various medical illness with enhanced angiogenesis. The molecular effects of HBO on visfatin under hypoxia are poorly understood. This study aimed to investigate the effect of HBO on visfatin in hypoxic human coronary arterial endothelial cells (HCAECs). HCAECs under chemical hypoxia (antimycin A, 0.01 mmol/L) were exposed to HBO (2.5 atmosphere absolute; ATA) for 2-4 hours. Western blot, real-time polymerase chain reaction, electrophoretic mobility shift assay, luciferase promoter activity, migration and tube formation assay, and in vitro glucose uptake were measured. Visfatin protein expression increased in hypoxic HCAECs with earlier angiotensin II (AngII) secretion and c-Jun N-terminal kinase (JNK) phosphorylation, which could be effectively suppressed by the JNK inhibitor (SP600125), AngII antibody or AngII receptor blocker (losartan). In hypoxic HCAECs, HBO further induced earlier expression of visfatin and AngII. Hypoxia significantly increased DNA-protein binding activity of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and visfatin. Hypoxia, hypoxia with HBO and exogenous addition of AngII also increased promoter transcription to visfatin; SP600125 and losartan blocked this activity. In HCAECs, glucose uptake, migration and tube formation were increased in the presence of hypoxia with HBO, but were inhibited by visfatin small interfering RNA, SP600125 and losartan. In conclusion, HBO activates visfatin expression and angiogenesis in hypoxic HCAECs, an effect mediated by AngII, mainly through the JNK pathway.