The rise in plasma
neopterin observed with increasing severity of
vascular disease is a strong
indicator of the inflammatory nature of
atherosclerosis. Plasma
neopterin originates as the oxidation product of
7,8-dihydroneopterin secreted by
gamma-interferon stimulated macrophages within
atherosclerotic plaques.
Neopterin is increasingly being used as a marker of
inflammation during clinical management of patients with a range of disorders including
atherosclerosis. Yet the role of 7,8-dihydroneopterin/
neopterin synthesis during the inflammatory process and plaque formation remains poorly understood and controversial. This is partially due to the unresolved role
oxidants play in
atherosclerosis and the opposing roles of 7,8-dihydroneopterin/
neopterin.
Neopterin can act as
pro-oxidant, enhancing
oxidant damage and triggering apoptosis in a number of different cell types.
Neopterin appears to have some cellular signalling properties as well as being able to chelate and enhance the reactivity of transition
metal ions during Fenton reactions. In contrast,
7,8-dihydroneopterin is also a radical scavenger, reacting with and neutralizing a range of
reactive oxygen species including
hypochlorite,
nitric oxide and peroxyl radicals, thus protecting
lipoproteins and various cell types including macrophages. This has led to the suggestion that
7,8-dihydroneopterin is synthesized to protect macrophages from the
oxidants released during
inflammation. The
oxidant/
antioxidant activity observed in vitro appears to be determined both by the relative concentration of these compounds and the specific chemistry of the in vitro system under study. How these activities might influence or modulate the development of
atherosclerotic plaque in vivo will be explored in this review.