Reactive Oxygen Species Mediated Impairment of the Glycolytic Switch Required Mesenchymal to Endothelial Transition in Hyperglycemia

Purpose: Endothelial Mesenchyme Transition plays a major role in fibrotic disorders associated with diabetes. Recently, the reverse phenomenon i.e., Mesenchyme Endothelial Transition (MEndoT) has been discovered as a physiological response to myocardial ischemia. MEndoT is characterized by fibroblast-derived endothelial cells (iECs) generation that contribute to angiogenesis in ischemic tissue. It is known that angiogenesis is impaired in diabetes and recent studies have also linked changes in energy metabolism with the cell fate determination. This study is to profile the metabolic change during MEndoT and to test whether hyperglycemia impairs MEndoT. Methods and Results: We have developed a small molecule based in vitro protocol for MEndoT. The iECs induced from this protocol manifest the genetical and functional profile of authentic ECs. Using the Seahorse technology, we discovered a …