Our researchers have developed a method which utilizes agents that activate σ1. The activation of σ1 encourages the metabolic production of ATP to be shifted from oxidative mechanisms to anaerobic glycolysis. Our data show for the first time that σ1 activation leads to enhanced glycolytic ATP production which is tightly linked to endothelial barrier integrity. Therefore, σ1 can be utilized as a novel therapeutic target for ameliorating endothelial barrier dysfunction caused by ischemia. This invention is applicable to any disease involving endothelial dysfunction, including but not limited to diabetes, peripheral vascular disease, heart disease, hypertension, venous thrombosis, insulin resistance, ischemic diseases of the gut, stroke, sepsis, chronic inflammatory diseases, and severe viral diseases.
The Identified Agent Enhanced Glycolytic ATP Production in Endothelial Cells