Mathematical modeling of shear stress-induced nitric oxide production in endothelial cell

The endothelial dysfunction occurs in the early stage of arteriosclerosis. The endothelium-derived nitric oxide (NO), produced by stimulating endothelial cells, causes the Flow-mediated Dilation (FMD) response. The FMD response provides useful information regarding the endothelial dysfunction. However, the FMD response also includes information on the tunica media function. In order to separate the response into these functions, we need a realistic model based on physiological pathways. Recently, Koo et al. proposed an NO production model in endothelial cells in-vitro. However, this model is not applicable to simulate the NO production on arbitrary stimuli. In the present study, we propose an improved model by introducing the variable structure in which rate constants of calcium dynamics is changed by the shear stress. To estimate the model parameters, we used the experimental data on the measurement of NO production characteristics. The proposed model well reproduced the experimental data. © 2014, Japan Soc. of Med. Electronics and Biol. Engineering. All rights reserved.