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Atherosclerosis/Lipoproteins

Caveolin-1 Plays a Critical Role in the Differentiation of Monocytes into Macrophages

Yi Fu, Xiao-Lei Moore, Man K. S. Lee, Manuel A. Fernández-Rojo, Marie-Odile Parat, Robert G. Parton, Peter J. Meikle, Dmitri Sviridov, Jaye P. F. Chin-Dusting
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https://doi.org/10.1161/ATVBAHA.112.254151
Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;ATVBAHA.112.254151
Originally published July 5, 2012
Yi Fu
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Xiao-Lei Moore
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Man K. S. Lee
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Manuel A. Fernández-Rojo
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Marie-Odile Parat
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Robert G. Parton
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Peter J. Meikle
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Dmitri Sviridov
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Jaye P. F. Chin-Dusting
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Abstract

Objective—Monocyte to macrophage differentiation is an essential step in atherogenesis. The structure protein of caveolae, caveolin-1, is increased in primary monocytes after its adhesion to endothelium. We explore the hypothesis that caveolin-1 plays a role in monocyte differentiation to macrophages.

Methods and Results—Both phorbol myristate acetate–induced THP-1 and colony stimulating factor–induced primary monocyte differentiation was associated with an increase in cellular caveolin-1 expression. Overexpression of caveolin-1 by transfection increased macrophage surface markers and inflammatory genes, whereas caveolin-1 knockdown by small interfering RNA or knockout reduced these. Also, caveolin-1 knockdown inhibited the differentiation–induced nuclear translocation of early growth response factor 1 (EGR-1) through ERK phosphorylation, further decreased the binding of EGR-1 to CD115 promoter, thus decreasing EGR-1 transcriptional activity. In functional assays, caveolin-1 inhibited transmigration but promoted phagocytosis in the monocyte–macrophage lineage. Decreasing caveolin-1 inhibited the uptake of modified low-density lipoprotein and reduced cellular lipid content. Finally, we showed that caveolin-1 knockout mice displayed less monocyte differentiation than wild-type mice and that EGR-1 transcription activity was also decreased in these mice because of the inhibition of ERK phosphorylation.

Conclusion—Caveolin-1 promotes monocyte to macrophage differentiation through the regulation of EGR-1 transcriptional activity, suggesting that phagocytic caveolin-1 may be critical for atherogenesis.

  • caveolin-1
  • monocyte differentiation
  • macrophages
  • early growth response factor 1
  • Received June 23, 2011.
  • Accepted June 25, 2012.
  • © 2012 American Heart Association, Inc.
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    Caveolin-1 Plays a Critical Role in the Differentiation of Monocytes into Macrophages
    Yi Fu, Xiao-Lei Moore, Man K. S. Lee, Manuel A. Fernández-Rojo, Marie-Odile Parat, Robert G. Parton, Peter J. Meikle, Dmitri Sviridov and Jaye P. F. Chin-Dusting
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;ATVBAHA.112.254151, originally published July 5, 2012
    https://doi.org/10.1161/ATVBAHA.112.254151

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    Caveolin-1 Plays a Critical Role in the Differentiation of Monocytes into Macrophages
    Yi Fu, Xiao-Lei Moore, Man K. S. Lee, Manuel A. Fernández-Rojo, Marie-Odile Parat, Robert G. Parton, Peter J. Meikle, Dmitri Sviridov and Jaye P. F. Chin-Dusting
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;ATVBAHA.112.254151, originally published July 5, 2012
    https://doi.org/10.1161/ATVBAHA.112.254151
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