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Cell and Tissue Research

, Volume 358, Issue 3, pp 821–831 | Cite as

Caveolin-1 regulates the anti-atherogenic properties of macrophages

  • Stephanos Pavlides
  • Jorge L. Gutierrez-Pajares
  • Sanjay Katiyar
  • Jean-François Jasmin
  • Isabelle Mercier
  • Rhonda Walters
  • Christos Pavlides
  • Richard G. Pestell
  • Michael P. Lisanti
  • Philippe G. Frank
Regular Article

Abstract

Atherosclerosis is a complex disease initiated by the vascular accumulation of lipoproteins in the sub-endothelial space, followed by the infiltration of monocytes into the arterial intima. Caveolin-1 (Cav-1) plays an essential role in the regulation of cellular cholesterol metabolism and of various signaling pathways. In order to study specifically the role of macrophage Cav-1 in atherosclerosis, we used Cav-1 −/− Apoe −/− mice and transplanted them with bone marrow (BM) cells obtained from Cav-1 +/+ Apoe −/− or Cav-1 −/− Apoe −/− mice and vice versa. We found that Cav-1 +/+ mice harboring Cav-1 −/− BM-derived macrophages developed significantly larger lesions than Cav-1 +/+ mice harboring Cav-1 +/+ BM-derived macrophages. Cav-1 −/− macrophages were more susceptible to apoptosis and more prone to induce inflammation. The present study provides clear evidence that the absence of Cav-1 in macrophage is pro-atherogenic, whereas its absence in endothelial cells protects against atherosclerotic lesion formation. These findings demonstrate the cell-specific role of Cav-1 during the development of this disease.

Keywords

Caveolin Caveolae Macrophage Atherosclerosis Lipoproteins Mouse 

Notes

Acknowledgments

The authors thank Dr. Iset Medina Vera for her technical support. P.G.F. was supported by grants from the Jane Barsumian/Mary Lyons Trust and the W.W. Smith Trust Fund. M.P.L. was supported by grants from the National Institutes of Health and the American Heart Association.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Stephanos Pavlides
    • 1
  • Jorge L. Gutierrez-Pajares
    • 2
    • 3
  • Sanjay Katiyar
    • 3
  • Jean-François Jasmin
    • 4
  • Isabelle Mercier
    • 4
  • Rhonda Walters
    • 5
  • Christos Pavlides
    • 2
  • Richard G. Pestell
    • 3
  • Michael P. Lisanti
    • 1
  • Philippe G. Frank
    • 2
    • 6
    • 7
  1. 1.Manchester Breast Centre & Breakthrough Breast Cancer Research Unit, Paterson Institute for Cancer Research, School of Cancer, Enabling Sciences and Technology, Manchester Academic Health Science CentreUniversity of ManchesterManchesterUK
  2. 2.Department of Stem Cell Biology & Regenerative Medicine, Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaUSA
  3. 3.Department of Cancer Biology, Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaUSA
  4. 4.Department of Pharmaceutical Sciences Philadelphia College of PharmacyUniversity of the SciencesPhiladelphiaUSA
  5. 5.Department of PathologyThomas Jefferson UniversityPhiladelphiaUSA
  6. 6.Department of Biochemistry and Molecular BiologyThomas Jefferson UniversityPhiladelphiaUSA
  7. 7.INSERM UMR1069 “Nutrition, Croissance et Cancer”, Faculté de MédecineUniversité François Rabelais de ToursTours CedexFrance

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