Mathematical model for shear stress dependent NO and adenine nucleotide production from endothelial cells.
Mathematical model for shear stress dependent NO and adenine nucleotide production from endothelial cells.
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剪切应力依赖性NO和腺嘌呤核苷酸产生的数学模型。
DOI：
10.1016/j.niox.2015.10.004
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发表时间：
2016-01-30
期刊：
影响因子：
--
通讯作者：
Jaron D
中科院分区：
文献类型：
--
作者：
Kirby PL;Buerk DG;Parikh J;Barbee KA;Jaron D
建立了一个平行板流动室装置的质量传递模型，用于预测培养的内皮细胞（EC）产生的一氧化氮（NO）和腺嘌呤核苷酸（ATP，ADP）的浓度，并研究了这三种化学物质的产生、降解和质量传递的净速率如何随壁面剪切应力（τw）的变化而变化。这些模拟提供了一个更好的理解与平行板流动室获得的实验结果，并允许定量分析之间的关系τw，腺嘌呤核苷酸浓度，和NO由EC产生。分析用腺苷三磷酸双磷酸酶改变ATP和ADP浓度后获得的实验数据，以量化NO产生速率（RNO）的变化。该模型可以预测腺苷三磷酸双磷酸酶不同亚型对ATP和ADP浓度的影响以及RNO的核苷酸依赖性变化。用腺苷三磷酸双磷酸酶预测ATP的减少，但由于ATP的降解模拟ADP的增加。我们发现，一个简单的比例关系RNO的一个组成部分的ATP和ADP的总和提供了一个密切的匹配拟合曲线的实验测量的变化RNO与腺苷三磷酸双磷酸酶。比例常数的估计值范围为每nM核苷酸浓度RNO增加0.0067至0.0321 μM/s，这取决于腺苷三磷酸双磷酸酶的同种型，在低τw（< 6 dyn/cm 2）时核苷酸对RNO的影响最大。
We developed a mass transport model for a parallel-plate flow chamber apparatus to predict the concentrations of nitric oxide (NO) and adenine nucleotides (ATP, ADP) produced by cultured endothelial cells (ECs) and investigated how the net rates of production, degradation, and mass transport for these three chemical species vary with changes in wall shear stress (τw). These simulations provide an improved understanding of experimental results obtained with parallel-plate flow chambers and allows quantitative analysis of the relationship between τw, adenine nucleotide concentrations, and NO produced by ECs. Experimental data obtained after altering ATP and ADP concentrations with apyrase were analyzed to quantify changes in the rate of NO production (RNO). The effects of different isoforms of apyrase on ATP and ADP concentrations and nucleotide-dependent changes in RNO could be predicted with the model. A decrease in ATP was predicted with apyrase, but an increase in ADP was simulated due to degradation of ATP. We found that a simple proportional relationship relating a component of RNO to the sum of ATP and ADP provided a close match to the fitted curve for experimentally measured changes in RNO with apyrase. Estimates for the proportionality constant ranged from 0.0067 to 0.0321 μM/s increase in RNO per nM nucleotide concentration, depending on which isoform of apyrase was modeled, with the largest effect of nucleotides on RNO at low τw (< 6 dyn/cm2).