EDN1 and endothelial dysfunction: Hyperglycemia-induced activation of protein kinase C (PKC) through an increase in diacylglycerol has a number of pathogenic effects such as decreased eNOS expression, increased ET-1 expression, increased plasminogen activator inhibitor-1 expression, increased transforming growth factor-β expression, NF-kB activation, and NADPH oxidase activation, leading to endothelial dysfunction.