Hyperglycemia and Endothelial Dysfunction in Atherosclerosis: Lessons from Type 1 Diabetes

Figure 3

Hyperglycemia-induced endothelial dysfunction and activation. (a) Hyperglycemia induces metabolic dysfunction through mitochondrial production of superoxide, resulting in PARP activation and subsequent altered glycolytic flux to enhance diacylglycerol production (DAG), methylglyoxal production, and hexosamine and polyol pathway activity. (b) Hyperglycemia-induced oxidative stress is further enhanced by metabolic overproduction of DAG and decreases in NADH⁺/reduced glutathione (GSH), as well as stimulation of the RAGE receptor. Oxidative stress reduces protective mediators (NO bioavailability) and enhances inflammatory transcription factor (NF-κB) activation resulting in inflammatory gene expression and leukocyte recruitment.