Vitamin E, 5-lipoxigenase and kidney disease (Chapter 5)

Atberosclerosis and its complications are leading causes of mortality in the developedworld. Vitamin E (α-tocopherol) is the main lipid-soluble antioxidant, and it modulatesthe expression of genes and the activity of enzymes involved in atherosclerosis. Inaddition to decreasing low-density lipoproteins (LDL) oxidation, vitamin E bas beenshown lo decrease the release of reactive oxygen species (ROS), to inhibit monocyteendothelialcell adhesion, and to reduce the release of proinflammatory andproatherogenic cytokines like inlerleukin Iß (IL-ß) and turnor necrosis factor α (TNF-α).More recently, we have sbown that vilamin E inhibits the activity of 5-lipoxygenase (5-LOX), a dioxygenase that converts arachidonic acid into leukolrienes and lipoxins. Inparticular, peripheral blood mononuclear cells (PBMC) contain an active 5-LOX, that isinvolved in LDL oxidation at the early stage of the atherosclerolic arterial lesion.Atherosclerosis is a leading cause of cardiovascular morbidity and mortality also in end-stagerenal disease (ESRD) patients. We have demonstrated that 5-LOX activity andmolecular expression are upregulaled in PBMC of patients on maintenance hemodialysis(HD), leading to enhanced membrane lipid peroxidation, ROS production, mitochondrialdamage and apoptosis of these cells. The data could explain at least in part the increasedsusceptibility of ESRD patients to atherosclerosis, compared to age-matched healthycontrols. Interestingly, vitamin E supply bas been shown to prevent oxidative stress andto increase LDL resistance to ex vivo oxidation in normal subjects and HD patients. Inparallel, 5-LOX activity, but not its gene expression, in PBMC was specifically inhibitedby vitamin E, both in vitro and in vivo.•[...]