Regulation of macrophage foam cell formation by αVβ3 integrin

Potential role in human atherosclerosis

Alexander S. Antonov, Frank D. Kolodgie, David H Munn, Ross G. Gerrity

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

The accumulation of macrophage foam cells in atherosclerotic lesions is associated with both initiation and progression of this disease. Scavenger receptors CD36 and SRA are the primary receptors responsible for conversion of macrophages into foam cells. Integrin αVβ3 plays a role in the differentiation of several cell types, but its involvement in the transition of macrophages into foam cells and the potential role of this receptor in atherosclerosis have not been examined. Using an in vitro model of single surface receptor activation by binding with an immobilized monoclonal antibody specific to αVβ3 integrin we show that ligation of αVβ3 integrin prevents differentiation of blood monocytes and macrophages into the foam cell phenotype via coordinate down-regulation of CD36 and SRA. This effect of αVβ3 integrin ligation can be reproduced by contact with endothelial cells, whereas the inhibition of αVβ3 receptor ligation restores the uptake of oxidized low-density lipoprotein. Moreover, we found that αVβ3 integrin is readily detected in situ on macrophages in early and advanced atherosclerotic lesions and that in vitro exposure to oxidized low-density lipoprotein up-regulates αVβ3 integrin expression. We hypothesize that αVβ3 integrin regulates macrophage functional maturation into foam cells in a persistent manner, and therefore, by targeting αVβ3 receptor it could potentially be possible to regulate progression of atherosclerosis in humans.

Original languageEnglish (US)
Pages (from-to)247-258
Number of pages12
JournalAmerican Journal of Pathology
Volume165
Issue number1
DOIs
StatePublished - Jan 1 2004

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Foam Cells
Integrins
Atherosclerosis
Macrophages
Ligation
Immobilized Antibodies
Scavenger Receptors
Disease Progression
Monocytes
Cell Differentiation
Up-Regulation
Down-Regulation
Endothelial Cells
Monoclonal Antibodies
Phenotype

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Regulation of macrophage foam cell formation by αVβ3 integrin : Potential role in human atherosclerosis. / Antonov, Alexander S.; Kolodgie, Frank D.; Munn, David H; Gerrity, Ross G.

In: American Journal of Pathology, Vol. 165, No. 1, 01.01.2004, p. 247-258.

Research output: Contribution to journalArticle

Antonov, Alexander S. ; Kolodgie, Frank D. ; Munn, David H ; Gerrity, Ross G. / Regulation of macrophage foam cell formation by αVβ3 integrin : Potential role in human atherosclerosis. In: American Journal of Pathology. 2004 ; Vol. 165, No. 1. pp. 247-258.
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