title: Caveolin-1 regulates the anti-atherogenic properties of macrophages.
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.
authors.affiliation: 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.
authors.forename: Stephanos
authors.initials: S
authors.lastname: Pavlides
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Gutierrez-Pajares
authors.forename: Sanjay
authors.initials: S
authors.lastname: Katiyar
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Jasmin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mercier
authors.forename: Rhonda
authors.initials: R
authors.lastname: Walters
authors.forename: Christos
authors.initials: C
authors.lastname: Pavlides
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Philippe G
authors.initials: PG
authors.lastname: Frank
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology*; D016026:Bone Marrow Transplantation; D051242:Caveolin 1 / Q000172:deficiency / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000097:blood; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051242:Caveolin 1; D016207:Cytokines; D008070:Lipopolysaccharides; D008074:Lipoproteins