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Diabetes 55:474-479, 2006
DOI: 10.2337/diabetes.55.02.06.db05-1078
© 2006 by the American Diabetes Association
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Complications

Statins Prevent Dextrose-Induced Endothelial Barrier Dysfunction, Possibly Through Inhibition of Superoxide Formation

Michael J. Haas, Mohamad H. Horani, Shant A. Parseghian, and Arshag D. Mooradian

From the Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, Missouri

Address correspondence and reprint requests to Arshag D. Mooradian, MD, Division of Endocrinology, Saint Louis University, 1402 S. Grand Blvd., St. Louis, MO 63104. E-mail: mooradad{at}slu.edu

Key Words: HUVEC, human umbilical endothelial cell • SSC, sodium chloride–sodium citrate

Statins may have favorable effects on endothelial barrier function, possibly through reduction of oxidative stress and modulation of expression of vasoactive proteins. The permeability of human umbilical endothelial cells in culture to a group of fluorescein isothiocyanate dextrans of different molecular weights were studied under various experimental conditions. Superoxide anion production was measured with an ethidium bromide fluorescence method. Cellular endothelin 1 mRNA and endothelin 1 in culture media were measured with Northern blots and enzyme immunoassays, respectively. Rosuvastatin (10 nmol/l) normalized the 500 mg/dl dextrose–induced permeability changes. Superoxide anion production induced by 500 mg/dl dextrose was inhibited by therapeutic concentrations of rosuvastatin or simvastatin (10 nmol/l), whereas the increased levels of cellular endothelin 1 mRNA and endothelin 1 in culture media was inhibited by supratherapeutic concentrations of statins (≥0.1 µmol/l). In conclusion, 1) endothelial cell barrier dysfunction occurs in cells treated with high concentrations of dextrose, 2) statin treatment of endothelial cells normalizes barrier permeability, and 3) the favorable effects of statins may be attributed to the inhibition of the dextrose-induced increase in superoxide anions, whereas inhibition of endothelin expression was observed only at supratherapeutic concentrations.


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Copyright © 2006 by the American Diabetes Association.