Does oxidative stress change ceruloplasmin from a protective to a vasculopathic factor?

Although ceruloplasmin (CP), a copper containing metalloenzyme, possesses antioxidant properties (e.g. ferroxidase activity), elevated circulating CP is associated with cardiovascular disease (CVD). This ambivalence is possibly due to the capacity of CP, via its coppers, to promote vasculopathic effects that include lipid oxidation, negation of nitric oxide bioactivity and endothelial cell apoptosis. In turn, these effects that are mediated by increased formation of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. There is also evidence that risk factors for CVD (in particular, diabetes mellitus and hyperhomocysteinaemia) may augment the vasculopathic impact of CP. In turn, it appears that ROS disrupt copper binding to CP, thereby impairing its normal protective function while liberating copper which in turn may promote oxidative pathology. The objective of this review, therefore, is to consider the epidemiology and pathophysiology of CP in relation to CVD, with particular emphasis on the relationship between CP and oxidative stress. (c) 2005 Elsevier Ireland Ltd. All rights reserved.