Oxysterols: a likely molecular link between hypercholesterolemia and pathology in humans

Oxysterols are a family of 27-carbon cholesterol oxidation derivatives that may be absorbed with the diet or originated endogenously. A number of oxysterols of pathophysiologic relevance display remarkable pro-inflammatory, pro-apoptotic, and pro-fibrogenic effects, generally sustained by their ability of being pro-oxidant through a net activation of cellular NAD(P)H oxidases. Further, stimulation of the MEK/ERK signaling pathway appears to be a common feature of the biochemical effects exerted by this class of compounds. Indeed, selective metabolic inhibitors of NAD(P)H oxidase and MAPK pathway might quench or even prevent the cytotoxic effects of pathological accumulation of cholesterol oxides in cells and tissues. Oxysterols are now considered to be potentially involved in the initiation and progression of major chronic diseases including atherosclerosis, neurodegenerative processes, inflammatory bowel disease.