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The vascular endothelial-cell simulation model had proposed in our previous studies. The study focused on internal voltage and ion clamp experiments in various elements of the model. These experiments confirmed the characteristics of the internal parts of the mathematical model and the calcium ion signal simulation conditions of the intact endothelial cell model. Although, the architecture of the electrophysiological model was established in intracellular clamp experiments, it was not clamped against extracellular ionic conditions to understand the cellular response to external stimuli. In this study, extracellular potassium ion concentration clamp experiments were used to stimulate different Cl-type and K-type endothelial cell models. In this experiment we found that significant depolarization occurs when the endothelial cell model of 100% GVRAC is clamped with approximately 10 mM of external potassium ions. In addition, other low-intensity GVRAC endothelial cell models produce varying degrees of membrane potential stimuli depolarization when clamped to extracellular potassium concentrations below 5 mM. The mathematical model also has a certain degree of ability to simulate the electrophysiological phenomena that occur in actual experiments in the process of simulating actual cases.
In the second phase of the study, we established a superoxide synthesis pathway led by lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) based on this endothelial cell electrophysiological model, and set up a PAF-R pathway that mimics the stimulation of calcium signaling. The mathematical model was able to simulate endothelial nitric oxide and superoxide biosynthesis changes in endothelial dysfunction induced by oxidized low-density lipoprotein (oxLDL) stimulation. The above biosynthesis mechanism is used to simulate the decrease of intracellular nitric oxide utilization rate when nitric oxide and superoxide are combined to synthesize Nitrite, and the independent endothelial cell apoptosis model established in this study can be used for comparison. Combine the results of the above studies to explore the concentration-time relationship between the various elements of these new pathways.
Through this model of endothelial dysfunction, we hope to improve the content that has not yet been added, and to explore the biological pathway in another dimension to gain a deeper understanding of the relevance of each component. We hope that this study will be helpful for pharmacological research.
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