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.
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