Autoimmune-mediated oxidative stress and endothelial dysfunction: implications of accelerated vascular injury in type I diabetes.
The pathogenesis of cardiovascular disease in the setting of type 1 diabetes is not well-defined. The hypothesis that hyperglycemia is largely responsible for vascular endothelial dysfunction, and ultimately atherosclerosis, continues to evolve. However, despite tight glucose control, a subset of patients still develop clinically significant occlusive disease. While the specific mechanisms of persistent vascular injury are not clear, an increasing body of evidence suggests a dysregulated autoimmune response may contribute to the development of vascular injury. That is, the same inflammatory response that is responsible for pancreatic beta-cell destruction may facilitate chronic vascular endothelial injury prior to the onset of hyperglycemia. Herein, we discuss (1) the clinical experience with tight glycemic control and the risk of cardiovascular disease in patients with type 1 diabetes; (2) the cellular mechanisms involved in vascular endothelial injury; and (3) the long-term clinical implications of autoimmune-mediated vascular disease and current treatment strategies.
Zimmerman
Michael A
MA
Division of Transplant Surgery, University of Colorado Health Sciences Center, Aurora, Colorado 80262, USA. michael.zimmerman@uchsc.edu
Flores
Sonia C
SC
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000276:immunology / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D018384:Oxidative Stress; D050378:T-Lymphocytes, Regulatory / Q000502:physiology