Application Abstract: Previous clinical researches have suggested that glucose control may decrease the risk of diabetic cardiovascular complications at early stage.However,the intensive glucose control cannot yield more reduction in the cardiovascular events.This phenomenon may be related to the metabolic memory in the progression of the endothelium dysfunction induced by diabetes.It suggests that it is crucial to select the suitable time to intervene the progression of metabolic memory.We hypothesize that the reversible stage of metabolic memory might be the best intervention timing.Metabolic memory can be improved if we learn this key stage and intervene metabolic memory with suitable method at this stage.The aim of this project is to find the key stage and factors of the metabolic memory by investigating the progression of the metabolic memory.In this project,the progression of metabolic memory is analyzed by the network balance model.Then,a mechanism based disease progression model for the metabolic memory is developed.Simulations are performed based on the network balance model and the mechanism based disease progression model to find the key stage and factors.Finally,the key stage and factors found by the simulation will be verified by experiments in vitro and in vivo.This project provides not only more insight into the key stage and factors of the metabolic memory but also basis for finding the new methods for preventing the metabolic memory in the progression of endothelium dysfunction induced by diabetes.
