Oxidative stress is
one factor that can trigger programmed cell death. Activated neutrophils responding to inflammatory stimulation produce
reactive oxygen species like superoxide free radicals
to kill invading bacteria, but these reactive oxygen species can also attack
endothelial cells lining the vascular wall and trigger apoptosis. Endothelial
cells also produce reactive oxygen species inside the cell that can contribute
to oxidative stress and apoptosis, such as during reperfusion injury following
ischemia. Superoxide dismutase
(SOD) converts highly reactive and damaging superoxide
free radicals to peroxides that are less reactive than superoxide
but stimulate apoptosis. The glutathione (GSH) peptide reducing agent removes
toxic metabolites and repairs damage created by reactive oxygen species.
Glutathione peroxidase (GPx),
for example, removes peroxides using glutathione as a reducing agent, and
glutathione reductase (GSR) regenerates reduced
glutathione. Inside the endothelial cell peroxide can be converted to hydroxyl
ions in the presence of iron. Peroxides and hydroxyl radicals activate NF-kB and activate expression of inflammatory genes including
adhesion molecules, TNF and IL-8. The apoptotic response of endothelial cells
to oxidative stress may be involved in the development and progression of
atherosclerosis