Insilico reaction kinetic model of shear stress induced eNOS activation in arterial endothelium

Blood vessels are constantly exposed to hemodynamic forces in the form of cyclic stretch and shear stress due to the pulsatile nature of blood flow. Endothelial cells (ECs) lining these blood vessels act as a sensing interface to transduce these hemodynamic forces or mechanical stimuli to intracellular signals. EC signaling leads to the production of nitric oxide (NO) that regulates the flow pressure through relaxation of smooth muscle. A theoretical frame work that captures the mechanics of vascular remodeling process along with intracellular signaling cascade can shed light in the process of adaptation and regulation of blood flow in these arteries. Towards this end, we have developed a detail mass action model of intracellular signaling, including shear induced eNOS activation, an enzyme that produces NO for signaling, leading to the regulation of NO production. We simulate shear-induced activation of eNOS in detail. We show that upon shear stimulus, concentration of GTP.G¿ increases instantly to 1.5 fold leading to increase in active eNOS to two fold. We further show that our approach is modular in that various pathways constituting the model of eNOS activation and smooth muscle relaxation can be included one-by-one.