Kirby Patrick L, Buerk Donald G, Parikh Jaimit, Barbee Kenneth A, Jaron Dov
School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA.
School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA.
Nitric Oxide. 2016 Jan 30;52:1-15. doi: 10.1016/j.niox.2015.10.004. Epub 2015 Oct 31.
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/cm(2)).
我们开发了一种用于平行板流动腔装置的传质模型，以预测培养的内皮细胞（ECs）产生的一氧化氮（NO）和腺嘌呤核苷酸（ATP、ADP）的浓度，并研究这三种化学物质的净产生率、降解率和传质率如何随壁面剪应力（τw）的变化而变化。这些模拟有助于更好地理解使用平行板流动腔获得的实验结果，并允许对τw、腺嘌呤核苷酸浓度和ECs产生的NO之间的关系进行定量分析。分析了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产生率（RNO）的变化。该模型可以预测不同同工型的腺苷三磷酸双磷酸酶对ATP和ADP浓度的影响以及RNO中核苷酸依赖性的变化。预计腺苷三磷酸双磷酸酶会使ATP减少，但由于ATP的降解，模拟出ADP会增加。我们发现，RNO的一个组成部分与ATP和ADP之和之间的简单比例关系与用腺苷三磷酸双磷酸酶实验测量的RNO变化的拟合曲线非常匹配。比例常数的估计值范围为每纳摩尔核苷酸浓度增加RNO 0.0067至0.0321 μM/s，这取决于所模拟的腺苷三磷酸双磷酸酶的同工型，在低τw（<6 dyn/cm²）时，核苷酸对RNO的影响最大。
