Class A scavenger receptors, macrophages, and atherosclerosis

Curr Opin Lipidol. 2001 Oct;12(5):489-95. doi: 10.1097/00041433-200110000-00003.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Arteriosclerosis / physiopathology*
  • CD36 Antigens / metabolism*
  • Disease Models, Animal
  • Foam Cells / metabolism*
  • Gene Deletion
  • Humans
  • Hyperlipidemias / physiopathology
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Immunologic / metabolism*
  • Receptors, LDL / metabolism
  • Receptors, Scavenger
  • Scavenger Receptors, Class A

Substances

  • CD36 Antigens
  • MSR1 protein, human
  • Msr1 protein, mouse
  • Receptors, Immunologic
  • Receptors, LDL
  • Receptors, Scavenger
  • Scavenger Receptors, Class A