TY - JOUR
T1 - Regulation of macrophage foam cell formation by αVβ3 integrin
T2 - Potential role in human atherosclerosis
AU - Antonov, Alexander S.
AU - Kolodgie, Frank D.
AU - Munn, David H.
AU - Gerrity, Ross G.
PY - 2004/7
Y1 - 2004/7
N2 - 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.
AB - 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.
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U2 - 10.1016/S0002-9440(10)63293-2
DO - 10.1016/S0002-9440(10)63293-2
M3 - Article
C2 - 15215180
AN - SCOPUS:3042690158
SN - 0002-9440
VL - 165
SP - 247
EP - 258
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -