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Caveolin-1 regulates the anti-atherogenic properties of macrophages |
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| Authors: | 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 |
| Institution: | 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 Centre, University of Manchester, Manchester, UK 2. Department of Stem Cell Biology & Regenerative Medicine, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA 3. Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA 4. Department of Pharmaceutical Sciences Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USA 5. Department of Pathology, Thomas Jefferson University, Philadelphia, PA, USA 6. Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA 7. INSERM UMR1069 “Nutrition, Croissance et Cancer”, Faculté de Médecine, Université Fran?ois Rabelais de Tours, 37032, Tours Cedex, France |
| 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. |
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