The research into the pathophysiology of
atherosclerosis has considerably increased our understanding of the disease complexity, but still many questions remain unanswered, both mechanistically and pharmacologically. Here, we provided evidence that the
pro-oxidant enzyme Prenylcysteine Oxidase 1 (PCYOX1), in the human atherosclerotic lesions, is both synthesized locally and transported within the subintimal space by proatherogenic
lipoproteins accumulating in the arterial wall during
atherogenesis. Further, Pcyox1 deficiency in
Apoe-/- mice retards atheroprogression, is associated with decreased features of lesion vulnerability and lower levels of lipid peroxidation, reduces plasma
lipid levels and
inflammation. PCYOX1 silencing in vitro affects the cellular
proteome by influencing multiple functions related to
inflammation, oxidative stress, and platelet adhesion. Collectively, these findings identify the
pro-oxidant enzyme PCYOX1 as an emerging player in
atherogenesis and, therefore, understanding the biology and mechanisms of all functions of this unique
enzyme is likely to provide additional therapeutic opportunities in addressing
atherosclerosis.