041 - Cholesterol oxidation products in the progression of atherosclerosis
Autore/i: G. Leonarduzzi, S. Gargiulo, P. Gamba, B. Sottero, C. Mascia, F. Biasi, G. Poli
Rivista: RIMeL - IJLaM, Vol. 6, N. 3-S1, 2010 (MAF Servizi srl ed.)
Oxysterols represent a family of 27-carbon cholesterol derivatives that may be absorbed with the diet or originated endogenously. These compounds are able to modulate various signaling pathways, by this way exerting a number of biochemical effects that include promotion of chronic inflammation, fibrosis and apoptotic cell death. Cholesterol oxidation products, as with the other oxidation products of the lipid moiety of plasma low density lipoproteins (LDL), are consistently found within the characteristic lesions of atherosclerosis. Of note, the challenge of cells of the macrophage lineage with a mixture of oxysterols like that detectable in hypercholesterolemic individuals leads to a marked overexpression of various inflammation-related molecules like TGF1 and MCP-1, but also of CD36 scavenger receptor. The possible up-regulation of these proteins within the atherosclerotic lesion indicates the ability of biologically relevant amounts of oxysterols to attract monocytic cells into the subintimal space and to stimulate their differentiation into macrophages with eventual formation of adherent foam cells. It is very likely that oxysterols make a significant contribution to the vascular changes occurring in atherosclerosis. They may be involved, besides foam cell formation, in all other key steps of this complex process, namely endothelial cell dysfunction and adhesion of circulating blood cells, deposition of extracellular matrix, and, in the unstable plaques, matrix degradation and apoptotic death of vascular cells.