Oxidized products of cholesterol: dietary and metabolic origin, and proatherosclerotic effects (review)

Cholesterol oxidation products, termed oxysterols, are increasingly considered of potential interest in the pathogenesis of atherosclerotic lesions. Of dietary or endogenous origin, oxysterols may occur in significant amounts in low density lipoprotein (LDL) particles, especially in hypercholesterolemic subjects. They likely contribute to the uptake of modified LDL by scavenger receptors and some of them finally accumulate in the subintimal space of major arteries; here cholesterol oxides may favor the perpetuation of a chronic inflammatory state, through their ability to trigger irreversible damage of vascular cells with consequent activation of phagocytes. Furthermore, practically all oxysterols of major pathophysiologic interest have been shown to markedly up-regulate expression and synthesis of adhesion molecules, inflammatory cytokines and chemokines. Cholesterol oxidation thus appears to be an important biochemical pathway through which it exerts toxic, inflammatory and finally atherogenic effects.