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Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation.
Applied Bionics and Biomechanics ( IF 1.8 ) Pub Date : 2019-04-14 , DOI: 10.1155/2019/6578492
Rebecca Lownes Urbano 1 , Swathi Swaminathan 2 , Alisa Morss Clyne 1, 2
Affiliation  

Arterial stiffness, which increases with aging and hypertension, is an independent cardiovascular risk factor. While stiffer substrates are known to affect single endothelial cell morphology and migration, the effect of substrate stiffness on endothelial monolayer function is less understood. The objective of this study was to determine if substrate stiffness increased endothelial monolayer reactive oxygen species (ROS) in response to protein kinase C (PKC) activation and if this oxidative stress then impacted adherens junction integrity. Porcine aortic endothelial cells were cultured on varied stiffness polyacrylamide gels and treated with phorbol 12-myristate 13-acetate (PMA), which stimulates PKC and ROS without increasing actinomyosin contractility. PMA-treated endothelial cells on stiffer substrates increased ROS and adherens junction loss without increased contractility. ROS scavengers abrogated PMA effects on cell-cell junctions, with a more profound effect in cells on stiffer substrates. Finally, endothelial cells in aortae from elastin haploinsufficient mice (Eln+/-), which were stiffer than aortae from wild-type mice, showed decreased VE-cadherin colocalization with peripheral actin following PMA treatment. These data suggest that oxidative stress may be enhanced in endothelial cells in stiffer vessels, which could contribute to the association between arterial stiffness and cardiovascular disease.

中文翻译:

刚性底物响应蛋白激酶C激活增强内皮氧化应激。

随着年龄增长和高血压而增加的动脉僵硬度是独立的心血管危险因素。虽然已知较坚硬的底物会影响单个内皮细胞的形态和迁移,但对底物刚度对内皮单层功能的影响知之甚少。这项研究的目的是确定底物硬度是否响应蛋白激酶C(PKC)活化而增加了内皮单层活性氧(ROS),并且该氧化应激是否进而影响粘附连接完整性。猪主动脉内皮细胞在不同硬度的聚丙烯酰胺凝胶上培养,并用佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)处理,该蛋白可刺激PKC和ROS,而不会增加放线菌素的收缩性。在较硬的底物上进行PMA处理的内皮细胞可增加ROS和粘附连接损失,而不会增加收缩力。ROS清除剂消除了PMA对细胞-细胞连接的影响,对更坚硬的底物上的细胞具有更深远的影响。最后,弹性蛋白单倍体不足小鼠的主动脉内皮细胞(Eln +/-)比野生型小鼠的主动脉更硬,显示在PMA处理后,VE-钙黏着蛋白与周围肌动蛋白的共定位降低。这些数据表明,氧化应激可能在较硬血管的内皮细胞中增强,这可能有助于动脉僵硬度与心血管疾病之间的联系。
更新日期:2019-04-14
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