Scavenger receptors and modified lipoproteins: Fatal attractions?

Lipoproteins modified by oxidation, glycation, alkylation, and nitration ar e generated by oxidative stress during inflammation, diabetes, and inadequa te supply of dietary antioxidants. A family of genes, the scavenger recepto rs, recognizes and internalizes modified lipoproteins, making them suscepti ble to degradation. Clearance of modified lipoproteins by scavenger recepto rs occurs mainly in macrophages, dendritic cells, and Kupffer cells of the liver. However, scavenger receptor expression also occurs in other cells, s uch as endothelial cells, aortic smooth muscle cells, neuronal cells, and k eratinocytes. Thus, the local clearance of oxidized low-density lipoprotein and the resolution of inflammatory processes mag rely in part on the expre ssion of scavenger receptors in "nonprofessional" phagocytes. Uptake of oxi dized low-density Lipoprotein, without an efficient machinery to degrade th em and uncontrolled expression of scavenger receptors, may lead to cellular deregulation, apoptosis, and formation of foam cells. Diseases accompanied by oxidation of lipoproteins, such as atherosclerosis, Alzheimer disease, glomerulosclerosis, ataxia with vitamin E deficiency: and possibly age-depe ndent lipofuscin deposition, may share a common pathogenetic feature. This review will focus on foam cell formation, mainly within the atherosclerotic lesion, and the possible involvement of aberrant regulation of the scaveng er receptor genes, To date, the regulatory mechanisms at the basis of scave nger receptor gene expression and their roles in atherosclerosis and other diseases are not well established, Knowledge on this subject could lead to a better understanding of the pathogenesis, prevention, and therapy of thes e diseases.