title: Sulfonylureas induce cholesterol accumulation in cultured human intimal cells and macrophages.
abstract: 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.
authors.affiliation: Institute of Experimental Cardiology, National Cardiology Research Center, Moscow, Russia.
authors.forename: I A
authors.initials: IA
authors.lastname: Sobenin
authors.forename: M A
authors.initials: MA
authors.lastname: Maksumova
authors.forename: E S
authors.initials: ES
authors.lastname: Slavina
authors.forename: M I
authors.initials: MI
authors.lastname: Balabolkin
authors.forename: A N
authors.initials: AN
authors.lastname: Orekhov
mesh_terms: 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*
chemical_list: D013453:Sulfonylurea Compounds; D002784:Cholesterol; D005907:Gliclazide; D005905:Glyburide; D005913:Glipizide