Differential sex-specific effects of oxygen toxicity in human umbilical vein endothelial cells.

Differential sex-specific effects of oxygen toxicity in human umbilical vein endothelial cells.
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氧毒性对人脐静脉内皮细胞的不同性别特异性影响。

DOI:
10.1016/j.bbrc.2017.03.058
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发表时间:
2017
影响因子:
3.1
通讯作者:
Lingappan,Krithika
Lingappan,Krithika
中科院分区:
生物学4区
文献类型:
--
作者:
Zhang,Yuhao;Lingappan,Krithika

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尽管支气管肺发育不良(BPD)的发病率存在性别特异性差异,但其背后的分子机制尚未完全了解。肺血管生成对于肺泡化是至关重要的,并且血管发育中的停滞不利地影响肺发育。人新生儿脐静脉内皮细胞(HUVECs)为内皮细胞生理和功能的研究提供了一个可靠的体外模型。将雄性和雌性HUVEC暴露于室内空气(21%O2,5%CO2)或高氧(95%O2,5%CO2)中长达72 h。分析细胞活力、增殖、H2 O2产生和血管生成。VEGF 2表达和NF-κ B通路调节的性别特异性差异被测量。与同样暴露的雌性细胞相比,雄性HUVEC具有降低的存活率、更大的氧化应激和血管生成损伤。在雄性和雌性HUVEC之间存在VEGF 2的差异表达,并且在高氧条件下雌性HUVEC中NF-κ B途径的激活更大。结果表明,高氧暴露后,雄性和雌性HUVEC在体外存在性别差异。由于内皮功能障碍在BPD的发病机制中起着重要作用,这些差异可以部分解释这种疾病发病率性别特异性差异背后的机制。
Despite the well-established sex-specific differences in the incidence of bronchopulmonary dysplasia (BPD), the molecular mechanism(s) behind these are not completely understood. Pulmonary angiogenesis is critical for alveolarization and arrest in vascular development adversely affects lung development. Human neonatal umbilical vein endothelial cells (HUVECs) provide a robustin vitromodel for the study of endothelial cell physiology and function. Male and Female HUVECs were exposed to room air (21% O2, 5% CO2) or hyperoxia (95% O2, 5% CO2) for up to 72 h. Cell viability, proliferation, H2O2production and angiogenesis were analyzed. Sex-specific differences in the expression of VEGFR2 and modulation of NF-kappa B pathway were measured.Male HUVECs have decreased survival, greater oxidative stress and impairment in angiogenesis compared to similarly exposed female cells. There is differential expression of VEGFR2 between male and female HUVECs and greater activation of the NF-kappa B pathway in female HUVECs under hyperoxic conditions. The results indicate that sex differences exist between male and female HUVECsin vitroafter hyperoxia exposure. Since endothelial dysfunction has a major role in the pathogenesis of BPD, these differences could explain in part the mechanisms behind sex-specific differences in the incidence of this disease.
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