Sex-Specific Response to Combinations of Shear Stress and Substrate Stiffness by Endothelial Cells In Vitro.

Sex-Specific Response to Combinations of Shear Stress and Substrate Stiffness by Endothelial Cells In Vitro.
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体外培养内皮细胞对剪切力和基质硬度组合的性别特异性反应。

DOI:
10.1002/adhm.202100735
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发表时间:
2021-09
影响因子:
10
通讯作者:
Allen JB
Allen JB
中科院分区:
工程技术1区
文献类型:
--
作者:
James BD;Allen JB

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通过使用一个完整的析因设计的实验,生物性别,剪切应力,和基板刚度对人脐静脉内皮细胞(HUVEC)的蔓延和YAP 1(YAP 1)活性的组合效应能够有效地进行评估。在剪切应力(0.5- 1.5Pa)和基底刚度(10-100 kPa)的范围内,雄性HUVEC小于雌性HUVEC。只有在足够的机械刺激下,它们才会扩散到相似的大小。更重要的是,YAP 1核定位在女性HUVEC是不变的机械刺激范围内的测试条件,而男性HUVEC的增加非线性增加剪切应力和基板刚度。HUVEC对剪切应力和基底硬度组合的性别特异性反应强化了将性别作为生物变量和多种机械刺激纳入实验的必要性,为精密生物材料的设计提供了信息,并为理解心血管疾病性二态性提供了见解。此外,这里还说明了不同的复杂机械微环境可以导致培养的内皮细胞中出现性别特异性表型和性别不变表型。
By using a full factorial design of experiment, the combinatorial effects of biological sex, shear stress, and substrate stiffness on human umbilical vein endothelial cell (HUVEC) spreading and Yes-associated protein 1 (YAP1) activity are able to be efficiently evaluated. Within the range of shear stress (0.5–1.5 Pa) and substrate stiffness (10–100 kPa), male HUVECs are smaller than female HUVECs. Only with sufficient mechanical stimulation do they spread to a similar size. More importantly, YAP1 nuclear localization in female HUVECs is invariant to mechanical stimulation within the range of tested conditions whereas for male HUVECs it increases nonlinearly with increasing shear stress and substrate stiffness. The sex-specific response of HUVECs to combinations of shear stress and substrate stiffness reinforces the need to include sex as a biological variable and multiple mechanical stimuli in experiments, informs the design of precision biomaterials, and offers insight for understanding cardiovascular disease sexual dimorphisms. Moreover, here it is illustrated that different complex mechanical microenvironments can lead to sex-specific phenotypes and sex invariant phenotypes in cultured endothelial cells.
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