Effect of simvastatin and fenofibrate on endothelium in Type 2 diabetes.
Statins and fibrates influence endothelial activity and consequently atherogenesis but the mechanisms are not well understood. Twenty Type 2 diabetic patients with dyslipidemia were treated 3 months with simvastatin (20 mg daily) and then 3 months with fenofibrate (200 mg daily) with 2 months of wash-out between the two treatments. Laboratory parameters of oxidative stress, fibrinolysis and endothelial function were evaluated before and at the end of each treatment period. The significant decrease in serum total and LDL-cholesterol concentrations (P<0.0001) caused by simvastatin was associated with an increase in serum N-acetyl-beta-glucosaminidase activity (P<0.001), ascorbic acid (P<0.001), plasminogen activator inhibitor (PAI-1) (P<0.01), vonWillebrand factor (P<0.05), E-selectin (P<0.01) and vascular endothelial growth factor (P<0.05) concentrations and with a decrease in plasma glutathione (P<0.01) levels. Fenofibrate caused a significant decrease in serum triglyceride concentration (P<0.0001) associated with a decrease in plasma malondialdehyde (P<0.001) and an increase in plasma PAI-1 (P<0.05) and P-selectin (P<0.05) concentrations. We conclude that simvastatin and fenofibrate interact, by different mechanisms, with oxidative stress, a key factor in the modification of fibrinolysis and endothelial function in Type 2 diabetes.
Skrha
Jan
J
Laboratory for Endocrinology and Metabolism, Faculty of Medicine 1, Czech Republic. jan.skrha@lfl.cuni.cz
Stulc
Tomás
T
Hilgertová
Jirina
J
Weiserová
Hana
H
Kvasnicka
Jan
J
Ceska
Richard
R
D000118:Acetylglucosaminidase / Q000097:blood / Q000187:drug effects; D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000097:blood; D002784:Cholesterol / Q000097:blood / Q000145:classification; D018153:Czech Republic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004334:Drug Administration Schedule; D019040:E-Selectin / Q000097:blood; D004727:Endothelium / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005342:Fibrinolysis / Q000187:drug effects; D005978:Glutathione / Q000097:blood; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D019821:Simvastatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000097:blood / Q000187:drug effects; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D024502:alpha-Tocopherol / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
D019040:E-Selectin; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D008315:Malondialdehyde; D002784:Cholesterol; D019821:Simvastatin; D013482:Superoxide Dismutase; D000118:Acetylglucosaminidase; D005978:Glutathione; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D011345:Fenofibrate