Adaptation of endothelial cells to physiologically-modeled, variable shear stress.
Adaptation of endothelial cells to physiologically-modeled, variable shear stress.
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DOI：
10.1371/journal.pone.0057004
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
McFetridge PS
中科院分区：
文献类型：
--
作者：
Uzarski JS;Scott EW;McFetridge PS
内皮细胞（EC）功能由血管壁处的可变血流动力学剪切应力模式介导，其中复杂的剪切应力曲线与基于代谢需求随时间变化的血流条件直接相关。这些更复杂和可变的剪切场与EC的相互作用尚未在血流动力学流动模型中表示。我们假设EC暴露于脉动剪切应力，其幅度和持续时间的变化，直接从心率的实时生理变化建模，将引起与其在血栓形成，止血和炎症中的关键作用相关的表型变化。在这里，我们设计了一个生理流量（PF）模型的基础上，在体内观察到的血流的短期时间变化，并将其与静态培养和稳定流（SF）在一个固定的脉冲频率为1.3 Hz。结果表明，基因调控的显着变化，作为一个功能的时间可变的流量，表明减少伤口表型的静止更有代表性。与SF下培养的细胞相比，在PF下培养的EC表现出显著更高的内皮一氧化氮合酶（eNOS）活性（PF：176.0±11.9 nmol/105 EC; SF：115.0±12.5 nmol/105 EC，p = 0.002）和更低的TNF-α诱导的HL-60白细胞粘附（PF：37±6 HL-60细胞/mm 2; SF：111±18 HL-60/mm 2，p = 0.003），这与更静止的抗炎和抗血栓形成表型一致。 体外模型越来越善于模仿自然生理学，并在此过程中阐明了驱动细胞功能的化学和物理线索的重要性。这些数据表明，在代谢需求的变化和随后的变化，灌注导致不断变化的剪切应力EC功能，以前没有被描述起着关键作用。
Endothelial cell (EC) function is mediated by variable hemodynamic shear stress patterns at the vascular wall, where complex shear stress profiles directly correlate with blood flow conditions that vary temporally based on metabolic demand. The interactions of these more complex and variable shear fields with EC have not been represented in hemodynamic flow models. We hypothesized that EC exposed to pulsatile shear stress that changes in magnitude and duration, modeled directly from real-time physiological variations in heart rate, would elicit phenotypic changes as relevant to their critical roles in thrombosis, hemostasis, and inflammation. Here we designed a physiological flow (PF) model based on short-term temporal changes in blood flow observed in vivo and compared it to static culture and steady flow (SF) at a fixed pulse frequency of 1.3 Hz. Results show significant changes in gene regulation as a function of temporally variable flow, indicating a reduced wound phenotype more representative of quiescence. EC cultured under PF exhibited significantly higher endothelial nitric oxide synthase (eNOS) activity (PF: 176.0±11.9 nmol/105 EC; SF: 115.0±12.5 nmol/105 EC, p = 0.002) and lower TNF-a-induced HL-60 leukocyte adhesion (PF: 37±6 HL-60 cells/mm2; SF: 111±18 HL-60/mm2, p = 0.003) than cells cultured under SF which is consistent with a more quiescent anti-inflammatory and anti-thrombotic phenotype. In vitro models have become increasingly adept at mimicking natural physiology and in doing so have clarified the importance of both chemical and physical cues that drive cell function. These data illustrate that the variability in metabolic demand and subsequent changes in perfusion resulting in constantly variable shear stress plays a key role in EC function that has not previously been described.
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DOI：
10.1161/atvbaha.108.165951
发表时间：
2008-12
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Hahn C;Schwartz MA
通讯作者：
Schwartz MA
影响因子：
20.1
作者：
Dai, Guohao;Vaughn, Saran;Gimbrone, Michael A., Jr.
通讯作者：
Gimbrone, Michael A., Jr.
DOI：
10.1152/ajpheart.01087.2006
发表时间：
2007-07-01
影响因子：
4.8
作者：
Himburg, Heather A.;Dowd, Scot E.;Friedman, Morton H.
通讯作者：
Friedman, Morton H.
DOI：
10.1073/pnas.1434429100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Chi, JT;Chang, HY;Brown, PO
通讯作者：
Brown, PO
DOI：
10.1115/1.3138276
发表时间：
1981-01-01
影响因子：
1.7
作者：
DEWEY, CF;BUSSOLARI, SR;DAVIES, PF
通讯作者：
DAVIES, PF