Format

Send to

Choose Destination
See comment in PubMed Commons below
Arterioscler Thromb Vasc Biol. 2011 Feb;31(2):458-63. doi: 10.1161/ATVBAHA.110.211789. Epub 2010 Nov 18.

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

Author information

1
Radboud University Nijmegen Medical Centre, Nijimegen Center for Molecular Life Sciences, Departments of Pharmacology and Toxicology, and Orthodontics and Oral Biology, Nijmegen, the Netherlands.

Abstract

OBJECTIVE:

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.

METHODS AND RESULTS:

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.

CONCLUSIONS:

Experimental hyperbilirubinemia is associated with a significant improvement of endothelial function in T2DM.

PMID:
21088253
DOI:
10.1161/ATVBAHA.110.211789
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center