Endothelial dysfunction, atherosclerosis and diabetes

The prevalence of early and accelerated development of atherosclerosis associated with high morbidity and mortality is markedly increased among individuals with diabetes and hypertension. Although the link between diabetes and vascular disease is not fully understood, loss of the modulatory role of the endothelium could be implicated in the pathogenesis of diabetic vascular complications. Diabetes-associated pathophysiologic conditions in the endothelium are modifications of lipoproteins, formation of advanced glycation end-products and circulating lipoprotein immune complexes, alteration of the nitric oxide pathway, and elevated levels of homocysteine. The main goals in restoration of endothelial function are optimal glycemic control, lipid lowering, cessation of smoking, normalization of elevated blood pressure, improvement of the NO-status, antioxidants for scavenging free oxygen radicals, normalization of homocysteine levels, antagonizing the hyperinsulinaemia, and regulation of rheology, respectively haemostasis to physiological levels. There is abundant evidence that some pharmacological agents exert direct beneficial effects on endothelium, suggesting that at least part of their therapeutic action is associated with improvement in endothelial dysfunction. A number of new findings about endothelial dysfunction may have potential clinical relevance.