Shepherd Robert D, Kos Stephanie M, Rinker Kristina D
Centre for Bioengineering Research and Education, University of Calgary, Calgary, AB, Canada.
Biorheology. 2009;46(6):529-38. doi: 10.3233/BIR-2009-0557.
Fluid dynamics strongly influences endothelial cell function, and participates in the localization of atherosclerotic plaques at blood vessel branches. We investigated the hypothesis that wild-type human aortic endothelial cells (HAEC) exposed to prolonged pulsatile flow stimulation have levels of phosphorylated mitogen-activated protein kinases (MAPK) that are significantly greater than those observed in statically grown cultures. HAEC were exposed to pulsatile laminar shear stress in a parallel-plate flow chamber and analyzed for levels of phosphorylated ERK, JNK and p38 at 1, 10 and 20 h. While some MAPK exhibited alternating patterns of phosphorylation, others were characterized by steady increases or unchanged profiles until the terminal (20 h) time point. However, at 20 h, each MAPK demonstrated an increase in phosphorylation versus statically cultivated cells. Further, 20 h cultures from 10 dyn/cm(2) pulsatile shear stress had higher levels of phosphorylation for each MAPK than those from 2 dyn/cm(2). The finding that MAPK species can be phosphorylated in response to a prolonged pulsatile shear stress in both a time and magnitude dependent manner is an interesting result that may help to explain how the differential behaviors observed between cells from different flow environments can be generated and maintained.
流体动力学对内皮细胞功能有强烈影响，并参与动脉粥样硬化斑块在血管分支处的定位。我们研究了这样一个假设：暴露于长时间脉动流刺激下的野生型人主动脉内皮细胞（HAEC）中，磷酸化丝裂原活化蛋白激酶（MAPK）的水平显著高于静态培养的细胞。将HAEC置于平行板流动腔中，使其暴露于脉动层流剪切应力下，并在1、10和20小时分析磷酸化ERK、JNK和p38的水平。虽然一些MAPK表现出磷酸化的交替模式，但其他MAPK的特征是在直至终末（20小时）时间点之前磷酸化水平持续增加或保持不变。然而，在20小时时，与静态培养的细胞相比，每种MAPK的磷酸化水平均有所增加。此外，来自10达因/平方厘米脉动剪切应力的20小时培养物中，每种MAPK的磷酸化水平均高于来自2达因/平方厘米的培养物。MAPK可响应长时间脉动剪切应力而发生磷酸化，且具有时间和强度依赖性，这一发现是一个有趣的结果，可能有助于解释如何产生和维持在不同流动环境下细胞间观察到的差异行为。
