A p53-Mdm2 Dynamical Model Induced by Laminar Shear Stress in Endothelial Cells

摘要

Atherosclerosis is a leading cause of death worldwide,and closely linked to the fate of the vascular endothelial cells.The endothelial cells can recognize the good flow and the bad flow.The laminar flow can suppress the proliferation of the endothelial cells to maintain cell homeostasis.The turbulence flow can induce the endothelial cell apoptosis,leading to the occurrence of atherosclerosis.The experimental results show that the laminar flow can activate the JNK kinase,and the JNK phosphorylates the p53 proteins.The transcription factor p53 is then able to activate genes expression related to cell arrest.Mdm2 is a negative regulator of p53.The interaction mechanism between p53 and Mdm2 is unknown in endothelial cells,and remains to be clarified by experiments.By assuming that there also exists the p53-Mdm2 negative feedback loop in endothelial cells,we developed a dynamical model for the p53-Mdm2 system driven by laminar shear stress in endothelial cells.The model shows that upon laminar shear stress the phosphorylated p53 exhibits the limit cycle oscillations via Hopf bifurcation.Such a stable periodic oscillations may activate the genes expression concerning the cell arrest,making the cell away from atherosclerosis.