title: Class A scavenger receptors, macrophages, and atherosclerosis.
abstract: The scope of this review is to discuss the new advances in our understanding of the role of scavenger receptor class A in the initiation and modulation of the atherosclerotic process. Through the approaches of gene manipulation in the mouse model, a substantial body of literature has accumulated that depicts scavenger receptor class A as a central player in atherogenesis. In studies of scavenger receptor class A overexpression in macrophages through bone marrow transplantation using transgenic donor material, recipient mice with hyperlipidemia caused either by apolipoprotein E or LDL receptor deficiency did not show convincing changes in the degree of atherosclerosis development compared with controls. Conversely, the deletion of the scavenger receptor class A gene in the mouse has shown, in a consistent and significant fashion, that this receptor serves a pro-atherogenic function under hyperlipidemic conditions, as both apolipoprotein E and LDL receptor-deficient mice had reduced atherosclerosis in the absence of scavenger receptor class A. In addition, we have recently shown that C57BL/6 mice are protected from diet-induced atherosclerosis when they lack scavenger receptor class A, and that the macrophage is the cell type responsible for the effect of scavenger receptor class A deficiency in reducing lesion formation in C57BL/6 and LDL receptor null mice. Together, these results demonstrate that macrophage scavenger receptor class A contributes significantly to atherosclerotic lesion formation, and suggest that the uptake of oxidized or modified lipoproteins by vessel wall macrophages is a central process in atherogenesis.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. macrae.linton@mcmail.vanderbilt.edu
authors.forename: M F
authors.initials: MF
authors.lastname: Linton
authors.forename: S
authors.initials: S
authors.lastname: Fazio
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D018955:CD36 Antigens / Q000378:metabolism*; D004195:Disease Models, Animal; D005487:Foam Cells / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D006949:Hyperlipidemias / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A
chemical_list: D018955:CD36 Antigens; C495139:MSR1 protein, human; C495140:Msr1 protein, mouse; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A