A new compound-specific pleiotropic effect of statins: modification of plasma gamma-tocopherol levels.

Gamma tocopherol (gamma-T) is a recognized peroxynitrite scavenger, reputedly metabolized via the cytochrome P450 3A4 (CYP3A4). In this study, we assessed whether equipotent LDL-lowering doses of statins with or without inhibitory activity on CYP3A4 differently affect gamma-T metabolism. Patients with ATP III criteria for statin use (n=35) were randomly allocated to treatment with simvastatin 20mg/day or pravastatin 40 mg/day.

Diversity and similarity in signaling events leading to rapid Cox-2 induction by tumor necrosis factor-alpha and phorbol ester in human endothelial cells.

Objective: This study examines whether cyclooxygenase 2 (Cox-2) synthesis in human endothelial cells involves different signaling pathways when induced by the proinflammatory cytokine tumor necrosis factor-alpha (TNF alpha) or by the tumor and angiogenic promoter phorbol ester (PMA). Moreover, the hypothesis that reactive oxygen species (ROS) and an altered redox status within the cell are fundamental steps for Cox-2 synthesis is verified.

Methods: Human endothelial cells isolated from umbilical vein (HUVEC) were exposed to PMA and TNF alpha and Cox-2 protein and mRNA levels were evaluated by Western blot and Real-Time Quantitative Reverse Transcription-PCR analysis.