Up-regulation of the fibrogenic cytokine TGF-beta1 by oxysterols: a mechanistic link between cholesterol and atherosclerosis.

Abstract

SPECIFIC AIMSOxidized low density lipoproteins (oxLDL) may contain variable amounts of oxysterols, i.e., 27-carbon products of cholesterol oxidation, which may become quantitatively important in hypercholesterolemic subjects. Oxysterols have been shown to exert a great many biochemical effects, but their potential action as lipid oxidation products on the macrophage expression of fibrogenic cytokines has not yet been investigated.PRINCIPAL FINDINGS1. A biologically compatible mixture of oxysterols is by far less cytotoxic than comparable amounts of individual oxysterolsThe potential cytotoxicity to cultured macrophages of a mixture of cholesterol oxidation products, whose composition is compatible with that of oxLDL in hypercholesterolemic patients or of comparable amounts of single sterols (7-ketocholesterol and unoxidized cholesterol), was initially evaluated. Cell viability and nuclear morphology were respectively checked by trypan blue test and fragment end labeling of DNA (TUNEL). A slight decrease i...