Cellular and molecular mechanisms of endothelial dysfunction in diabetes

In healthy individuals, the vascular endothelium regulates an intricate balance of factors that maintain vascular homeostasis and normal arterial function. Functional disruption of the endothelium is known to be an early event that underlies the development of subsequent cardiovascular disease (CVD) including atherosclerosis and coronary heart disease. In addition, the rising global epidemic of type 2 diabetes is a significant problem conferring a significantly higher risk of CVD to individuals in whom endothelial dysfunction is also notable. This review first summarises the role of endothelium in health and explores and evaluates the impact of diabetes on endothelial function. The characteristic features of insulin resistance and other metabolic disturbances that may underlie long-term changes in vascular endothelial function (metabolic memory) are described along with proposed cellular, molecular and epigenetic mechanisms. Through understanding the underlying mechanisms, novel targets for future therapies to restore endothelial homeostasis and ‘drive’ a reparative cellular phenotype are explored.