Objective: Enhanced production of reactive oxygen and/or nitrogen species in biological tissues
leads to oxidative and nitrative stress, a general pathophysiological phenomenon playing a role in the development
of various human diseases including cardiovascular and neurological disorders.
Method: Reactive oxygen and/or nitrogen species interact with lipids, DNA and proteins via oxidative or radical-
mediated reactions, potentially leading to cell damage or death. Proteoglycans are among the most important
structural and functional macromolecules in most tissues. The chemical structure of these molecules consist
of a core protein onto which one or more negatively charged glycosaminoglycan (GAG) chain(s) are covalently
attached. Interaction of proteoglycans with oxidative/nitrative stress has been demonstrated in various
experimental systems. In this review, we discuss the modulatory effects of proteoglycans on tissue oxidative/
nitrative stress and consequent cellular function especially in cardiovascular and neurological disorders.
Conclusion: Proteoglycans have been implicated in both deleterious and potentially cytoprotective mechanisms.
The protective mechanisms include chelation of positively charged transitional metal ions (e.g. iron and
copper), scavenging superoxide anions by extracellular superoxide dismutase, building pericellular net and
mediation of signal transduction pathways. Although these results may implicate proteoglycans as potential
therapeutic targets, more research should be done to better explore proteoglycans as modulators of reactive
oxygen/nitrogen species and to determine their possible therapeutic value in disorders accompanied by oxidative/