Participation of macrophages in atherosclerotic lesion morphology in LDLr-/- mice.

  • Schiller N
  • Black A
  • Bradshaw G
 et al. 
  • 17


    Mendeley users who have this article in their library.
  • 16


    Citations of this article.


Lystbeige (beige) mice crossed with LDL receptor-deficient (LDLr-/-) mice had a distinct atherosclerotic lesion morphology that was not observed in LDLr-/- mice. This morphology is often associated with a stable plaque phenotype. We hypothesized that macrophage expression of the beige mutation accounted for this distinct morphology. Cultured bone marrow-derived macrophages from LDLr-/- and beige,LDLr-/- mice were compared for their ability to accumulate cholesterol, efflux cholesterol, migrate in response to chemotactic stimuli through Matrigel-coated membranes, and express matrix metalloproteinase 9 (MMP9). No differences in cholesterol metabolism were identified. Beige,LDLr-/- macrophage invasion in vitro appeared to be less than LDLr-/- macrophage invasion but did not achieve significance. Nevertheless, tumor necrosis factor-alpha-induced MMP9 expression, secretion, and enzymatic activity of beige,LDLr-/- macrophages were all significantly decreased compared with those of LDLr-/- macrophages (P < 0.05). For in vivo analyses of macrophage function, bone marrow transplantation (BMT) studies were performed. LDLr-/- mice and beige,LDLr-/- mice were irradiated and reconstituted with wild-type or beige bone marrow from mice expressing green fluorescent protein (GFP). Identification of GFP cells provided for direct identification of donor-derived cells within lesions. Only expression of the beige mutation in the BMT recipients altered the macrophage location and collagen content of the lesions. These results suggested that impaired macrophage function by itself did not account for the stable lesion morphology of beige,LDLr-/- double-mutant mice.

Author-supplied keywords

  • Animals
  • Arteriosclerosis
  • Arteriosclerosis: metabolism
  • Cholesterol
  • Cholesterol: metabolism
  • Genes, Reporter
  • Macrophages
  • Macrophages: enzymology
  • Macrophages: metabolism
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 9: metabolism
  • Mice
  • Receptors, LDL
  • Receptors, LDL: deficiency
  • Receptors, LDL: genetics
  • Receptors, LDL: metabolism
  • Sinus of Valsalva
  • Sinus of Valsalva: pathology

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Natalie K Schiller

  • Audrey S Black

  • Gary P Bradshaw

  • David J Bonnet

  • Linda K Curtiss

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free