Details

Autor(en) / Beteiligte

• Dekker, Douwe
• Dorresteijn, Mirrin J
• Pijnenburg, Margot
• Heemskerk, Suzanne
• Rasing-Hoogveld, Anja
• Burger, David M
• Wagener, Frank A D T G
• Smits, Paul

Titel

The bilirubin-increasing drug atazanavir improves endothelial function in patients with type 2 diabetes mellitus

Ist Teil von

• Arteriosclerosis, thrombosis, and vascular biology, 2011-02, Vol.31 (2), p.458-463

Ort / Verlag

United States

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• In type 2 diabetes mellitus (T2DM), oxidative stress gives rise to endothelial dysfunction. Bilirubin, a powerful endogenous antioxidant, significantly attenuates endothelial dysfunction in preclinical experiments. The Gilbert syndrome is accompanied by a mild and lifelong hyperbilirubinemia and associated with only one third of the usual cardiovascular mortality risk. The hyperbilirubinemia caused by atazanavir treatment closely resembles the Gilbert syndrome. We thus hypothesized that treatment with atazanavir would ameliorate oxidative stress and vascular inflammation and improve endothelial function in T2DM. In a double-blind, placebo-controlled crossover design, we induced a moderate hyperbilirubinemia by a 3-day atazanavir treatment in 16 subjects experiencing T2DM. On the fourth day, endothelial function was assessed by venous occlusion plethysmography. Endothelium-dependent and endothelium-independent vasodilation were assessed by intraarterial infusion of acetylcholine and nitroglycerin, respectively. Atazanavir treatment induced an increase in average bilirubin levels from 7 μmol/L (0.4 mg/dL) to 64 μmol/L (3.8 mg/dL). A significant improvement in plasma antioxidant capacity (P<0.001) and endothelium-dependent vasodilation (P=0.036) and a decrease in plasma von Willebrand factor (P=0.052) were observed. Experimental hyperbilirubinemia is associated with a significant improvement of endothelial function in T2DM.