Increased superoxide anion formation in endothelial cells during hyperglycemia: an adaptive response or initial step of vascular dysfunction?

• Published in: Diabetes research and clinical practice Vol. 45; no. 2; pp. 153 - 160
• Main Authors: Graier, Wolfgang F., Posch, Karla, Fleischhacker, Eleonore, Wascher, Thomas C., Kostner, Gert M.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01-09-1999; Elsevier Science
• Subjects: Adaptation, Physiological; Animals; Aorta; Arteries; Associated diseases and complications; Biological and medical sciences; Ca 2+ signalling; Calcium - metabolism; Cells, Cultured; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - etiology; Diabetic Angiopathies - physiopathology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelial cells; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiology; Female; Free radicals; Glucose - pharmacology; Glycated LDL; Hyperglycemia - metabolism; Medical sciences; Models, Cardiovascular; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; Nitric oxide; Nitric Oxide - metabolism; Signal Transduction; Space life sciences; Superoxides - metabolism; Swine; Uterus - blood supply; Xanthine - pharmacology; Xanthine Oxidase - pharmacology; Austria; Europe; Glycated LDL; Free radicals; Ca 2+ signalling; Nitric oxide; Endothelial cells; Endocrinopathy; Endothelial cell; Pathogenesis; Diabetes mellitus; Cardiovascular disease; Biosynthesis; Biological activity; Vascular disease; Anions; Concomitant disease; Hyperoxides; Vasomotricity; Animal; Atherosclerosis
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/S0168-8227(99)00045-5

In diabetes mellitus, the risk for cardiovascular complications and development of atherosclerosis is increased compared with healthy individuals. Recently evidence was provided that increased production of superoxide anions occurs in endothelial cells during hyperglycemia. In order to evaluate the potential impact of the enhanced formation of this oxygen radical for vascular cell dysfunction and its role in tissue adaptation, it is essential to assess the effect of superoxide anions on endothelial cell function. Here, we present new data and review our previous work on the effects of superoxide anions on endothelial vascular function, such as intracellular Ca
2+ signal cascade, formation and bioactivity of nitric oxide. Based on the presented data we discuss superoxide anion production as a two faced phenomenon. In lower concentrations, superoxide anions are mediators of an endothelium adaptation to ensure endothelial vasomotion control. However, in higher concentrations superoxide anions disrupt endothelial-smooth muscle crosstalk resulting in vessel wall dysfunction and vascular wall dysfunction.