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Diabetes 53:2950-2959, 2004
© 2004 by the American Diabetes Association, Inc.

Leukocyte-Derived Myeloperoxidase Amplifies High-Glucose—Induced Endothelial Dysfunction Through Interaction With High-Glucose—Stimulated, Vascular Non—Leukocyte-Derived Reactive Oxygen Species

Chunxiang Zhang, Jian Yang, and Lisa K. Jennings

From the Vascular Biology Center of Excellence, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee

Vascular non–leukocyte-derived reactive oxygen species (ROS), such as superoxide and hydrogen peroxide (H2O2), have emerged as important molecules in diabetic endothelial dysfunction. In addition, leukocyte-derived myeloperoxidase (MPO) has been implicated in vascular injury, and its injury response is H2O2 dependent. It is well known that MPO can use leukocyte-derived H2O2; however, it is unknown whether the vascular-bound MPO can use high-glucose–stimulated, vascular non–leukocyte-derived H2O2 to induce diabetic endothelial dysfunction. In the present study, we demonstrated that MPO activity is increased in vessels from diabetic rats. In high-glucose–incubated rat aortas and in carotid arteries from rats with acute hyperglycemia, vascular-bound MPO utilized high-glucose–stimulated H2O2 to amplify the ROS-induced impairment of endothelium-dependent relaxation via reduction of nitric oxide bioavailability. Hypochlorous acid (HOCL)-modified LDL, a specific biomarker for the MPO/HOCL/chlorinating species pathway, was detected in LDL- and MPO-bound vessels with high-glucose–stimulated H2O2. The results suggest that vascular-bound MPO could use high-glucose–stimulated H2O2 to amplify high-glucose–induced injury in the vascular wall. MPO/H2O2/HOCL/chlorinating species may represent an important pathway in diabetes complications and a new mechanism in phagocyte- and systemic infection–induced exacerbation of diabetic vascular diseases.

Address correspondence and reprint requests to Chunxiang Zhang, MD, PhD, Vascular Biology Center of Excellence, Department of Medicine, University of Tennessee Health Science Center, 956 Court Ave., Coleman Bldg., H300, Memphis, TN 38163. E-mail: czhang{at}utmem.edu


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Copyright © 2004 by the American Diabetes Association.