Background-Antidiabetic thiazolidinediones (TZDs), like rosiglitazone or pioglitazone, improve endothelial function in patients with type 2 diabetes or metabolic syndrome, but it is currently unknown, whether these beneficial effects of TZDs depend on their metabolic action or may be caused by direct effects on the endothelium. Therefore, the present study examined whether short-term rosiglitazone treatment influences endothelium-dependent vasodilation as well as serum levels of vascular

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... biomarkers in healthy, nondiabetic subjects. Methods and Results-Short-term treatment (21 days) of healthy subjects (nϭ10) did not significantly change blood glucose levels or lipid profile. In contrast, rosiglitazone significantly increased flow-mediated, endothelium-dependent vasodilation already within the first day from 5.3Ϯ2.7% at baseline to 7.8Ϯ2.6%, further increasing it to 9.4Ϯ3.0% at day 21. In addition, the early improvement of endothelium-dependent vasodilation was paralleled by a rapid reduction of serum levels of the biomarkers C-reactive protein (CRP), serum amyloid A (SAA), and sE-selectin. Moreover, after drug withdrawal all markers remained suppressed for the whole follow-up period of 7 days. In contrast, rosiglitazone treatment did not significantly affect tumor necrosis factor (TNF)-␣, interleukin (IL)-6, sICAM-1, sVCAM-1, and sCD40L levels. Conclusions-Our study suggests a direct effect of TZD treatment on endothelial function and inflammatory biomarkers of arteriosclerosis, promoting the concept that TZDs, independent of their metabolic action, may exhibit protective effects in the vessel wall. (Arterioscler Thromb Vasc Biol. 2005;25:1804-1809.)