Sulfonylureas induce cholesterol accumulation in cultured human intimal cells and macrophages.
Using primary cultures of human smooth muscle intimal cells and mouse peritoneal macrophages it was demonstrated that oral hypoglycemic agents, sulfonylurea derivatives, at concentrations 10(-5)-10(-4) mol/l caused significant (by 25%-60%) intracellular total cholesterol accumulation. This in vitro atherogenic effect was confirmed in an ex vivo model. Sera from Type 2 diabetic patients, taken after sulfonylurea administration, acquired the ability to induce cholesterol accumulation in cultured cells. This enhanced atherogenic effect of patients' sera was observed for the next 2-4 h following the treatment and corresponded well to the pharmacokinetic characteristics of the tested drugs. The results suggest that sulfonylureas may exert a direct atherogenic action at the level of arterial cells, by increasing intracellular cholesterol content.
Sobenin
I A
IA
Institute of Experimental Cardiology, National Cardiology Research Center, Moscow, Russia.
Maksumova
M A
MA
Slavina
E S
ES
Balabolkin
M I
MI
Orekhov
A N
AN
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005907:Gliclazide / Q000494:pharmacology; D005913:Glipizide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D017539:Tunica Intima / Q000378:metabolism*
D013453:Sulfonylurea Compounds; D002784:Cholesterol; D005907:Gliclazide; D005905:Glyburide; D005913:Glipizide