The endothelium releases multiple mediators, not only regulators of vasomotor function but also important physiological and pathophysiological inflammatory mediators. Endothelial dysfunction is caused by chronic exposure to various stressors such as oxidative stress and modified low-density lipoprotein (LDL) cholesterol, resulting in impaired nitric oxide (NO) production and chronic inflammation. Biomechanical forces on the endothelium, including low shear stress from disturbed blood flow and hypertension, are also important causes of endothelial dysfunction. These processes seem to be augmented in patients with Diabetes. In states of insulin resistance and in type 2 Diabetes insulin signalling is impaired. Increased vascular inflammation, including enhanced expression of inter-leukin-6 (IL-6), vascular cellular adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein (MCP-1) are observed, as is a marked decrease in NO bioavail-ability. Furthermore, hyperglycaemia leads to increased formation of advanced glycation end products (AGE), which quench NO and impair endothelial function.
In summary, during the development of diabetes a number of biochemical and mechanical factors converge on the endothelium, resulting in endothelial dysfunction and vascular inflammation. In the presence of insulin resistance, these processes are potentiated and they provide a basis for the macrovascular disease seen in diabetes.
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