Role of vascular reactive oxygen species in development of vascular abnormalities in diabetes

Abstract

Macrovascular and microvascular diseases are currently the principal causes of morbidity and mortality in patients with diabetes. Oxidative stress has been postulated to be a major contributor to the pathogenesis of these events. There is considerable evidence that many biochemical pathways adversely affected by hyperglycemia and other substances that are found at elevated levels in diabetic patients are associated with the generation of reactive oxygen species, ultimately leading to increased oxidative stress in a variety of tissues. In the absence of an appropriate compensation by the endogenous antioxidant defense network, increased oxidative stress leads to the activation of stress-sensitive intracellular signaling pathways and the formation of gene products that cause cellular damage and contribute to the late complications of diabetes. It has recently been suggested that diabetic subjects with vascular complications may have a defective cellular antioxidant response against the oxidative stress generated by hyperglycemia. This raises the concept that antioxidant therapy may be of great interest in these patients. Although our understanding of how hyperglycemia-induced oxidative stress ultimately leads to tissue damage has advanced considerably in recent years, effective therapeutic strategies to prevent or delay the development of this damage remain limited. Thus, further investigations of therapeutic interventions to prevent or delay the progression of diabetic vascular complications are needed.