Diabetes and Atherosclerosis

This review summarizes pathogenic mechanisms leading to the development of atherosclerosis in diabetes. Contributing factors to endothelial dysfunction including nitric oxide, prostaglandins, oxidative stress, and pro-inflammatory mediators as well as hemodynamic flow changes are described. How factors contributing to endothelial dysfunction lead to changes in lipoprotein levels and to modification of lipoproteins as well as formation of modified lipoprotein immune complexes and how that contribute to foam cell formation is also detailed. New chapters were added on the novel role of sphingolipids in the development of atherosclerosis in diabetes and how microRNAs can influence the several pathogenic mechanisms leading to accelerated development of atherosclerosis in diabetes. The inflammatory component of atherosclerosis was also reviewed by examining macrophage activation by modified lipoproteins and modified LDL immune complexes, reviewing release of cytokines and growth factors and atheroma expansion as well as metalloproteinases and plaque rupture. Finally, thrombi formation and alterations in platelet aggregation and abnormalities in the clotting and fibrinolytic system were discussed. Overall this chapter offers an update on the contributing factors and mechanisms leading to accelerated development of atherosclerosis in diabetes and provides a glimpse on the complexity and multifactorial nature of the process.