A mathematical model of the cytosolic-free calcium response in endothelial cells to fluid shear stress.
A mathematical model of the cytosolic-free calcium response in endothelial cells to fluid shear stress.
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DOI：
10.1073/pnas.94.8.3726
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发表时间：
1997-04
影响因子：
11.1
通讯作者：
Theodore F. Wiesner;B. C. Berk;Androbertm . Nerem
中科院分区：
文献类型：
--
作者：
Theodore F. Wiesner;B. C. Berk;Androbertm . Nerem
内皮细胞对流动刺激的反应中重要的是无胞质钙瞬变。这些瞬变是由多种因素介导的，包括血源性激动剂、细胞外钙和流体施加的剪切力。已经开发了一个数学模型来描述剪切应力向第二信使细胞质钙的识别和转导。剪切应力通过至少两种方式调节钙反应。首先，激动剂向细胞表面的传质通过灌注而增强，因此与剪切应力有关。其次，细胞膜对细胞外钙的渗透性在暴露于剪切应力时增加。灌注液中激动剂的质量平衡与先前发表的钙动力学模型相结合。计算表明瞬态从传输限制移动到动力学限制的流动区域。参数研究表明过程中每个步骤对时间进程的不同贡献。这些步骤包括形成激动剂浓度边界层的时间、受体激活以及从细胞内储存的钙的动员。推测外源钙通过剪切应力门控离子通道进入细胞。该模型预测钙流入量对剪切应力的 S 形依赖性。瞬态峰值主要由激动剂途径决定，而平台水平则由钙流入控制。该模型预测了生理相关流量范围内钙瞬变的调制以及相关的剪切应力。这意味着血流动力学对于调节内皮生物学很重要。
Important among the responses of endothelial cells to flow stimuli are cytosolic-free calcium transients. These transients are mediated by several factors, including blood-borne agonists, extracellular calcium, and fluid-imposed shear forces. A mathematical model has been developed describing the recognition and transduction of shear stress to the second messenger cytosolic calcium. Shear stress modulates the calcium response via at least two modalities. First, mass transfer of agonist to the cell surface is enhanced by perfusion and is thus related to shear stress. Second, the permeability of the cell membrane to extracellular calcium increases upon exposure to shear stress. A mass balance for agonist in the perfusate is coupled to a previously published calcium dynamics model. Computations indicate a flow region where the transient moves from transport limited to kinetically limited. Parametric studies indicate distinct contributions to the time course by each step in the process. These steps include the time to develop the concentration boundary layer of agonist, receptor activation, and the mobilization of calcium from intracellular stores. Exogenous calcium is presumed to enter the cell via shear stress-gated ion channels. The model predicts a sigmoidal dependence of calcium influx upon shear stress. The peak value of the transient is determined largely by the agonist pathway, whereas the plateau level is governed by calcium influx. The model predicts the modulation of the calcium transient in the physiologically relevant range of flow and the associated shear stress. This implies that hemodynamics is important in regulating endothelial biology.