Heme oxygenase-1 counteracts contrast media-induced endothelial cell dysfunction (855.1)

Endothelial cell (EC) dysfunction contributes to the pathogenesis of contrast media (CM)-induced acute kidney injury, which is a major adverse event following coronary angiography. In this study, we evaluated the effect of CM on human EC proliferation, migration, and inflammation, and determined if heme oxygenase-1 (HO-1) influences the biological actions of CM. We found that three distinct iodine-based CM, including high-osmolar (diatrizoate), low-osmolar (iopamidol), and iso-osmolar (iodixanol), stimulated the expression of HO-1 protein and mRNA. The induction of HO-1 was dependent on the concentration and duration of CM exposure and associated with an increase in NF-E2-related factor-2 (Nrf2) activity and reactive oxygen species (ROS) production. CM also stimulated HO-1 promoter activity and this was prevented by mutating the antioxidant responsive element or by overexpressing dominant-negative Nrf2. In addition, the CM-mediated induction of HO-1 and activation of Nrf2 was abolished by N-acetyl-L-cyste...