title: Caveolin-1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T-cell response.
abstract: Caveolin-1 plays a crucial role in atherosclerosis, which is mainly attributed to its effects on low-density-lipoprotein (LDL) transcytosis. However, caveolin-1 has also been implicated in the regulation of inflammation. We investigated the effects of caveolin-1 deficiency in atherosclerosis with its accompanying changes in plaque- and lymphoid-related immunology and inflammation. Cav1(-/-)Apoe(-/-) mice exhibited a 15-fold reduction in plaque size with plaques containing fewer macrophages, T cells, and neutrophils. Intravital microscopy revealed 83% less leukocyte adhesion to the vessel wall in Cav1(-/-)Apoe(-/-) mice, which could be attributed to reduced endothelial chemokine ligand-2 (CCL-2/MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. Caveolin-1 deficiency resulted in a 57% increase in regulatory T cells and a 4% decrease in CD4(+) effector T cells in lymphoid organs. Bone marrow transplantations revealed that Cav1(-/-)Apoe(-/-) mice receiving Cav1(+/+)Apoe(-/-) or Cav1(-/-)Apoe(-/-) bone marrow presented 4- to 4.5-fold smaller plaques with no additional phenotypic changes. In contrast, atherosclerosis was not affected in Cav1(+/+) Apoe(-/-) recipients receiving Cav1(-/-)Apoe(-/-) or Cav1(+/+) Apoe(-/-) bone marrow. However, the presence of Cav1(-/-) Apoe(-/-) bone marrow was associated with an anti-inflammatory T-cell profile. Our study reveals that nonhematopoietic caveolin-1 determines plaque size, whereas hematopoietic caveolin-1 regulates lymphoid immune-modulation. However, both are required for phenotypic modulation of plaques.
authors.affiliation: Department of Pathology, Cardiovascular Research Institute Maastricht, University Maastricht, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands. david.engel@maastrichtuniversity.nl
authors.forename: David
authors.initials: D
authors.lastname: Engel
authors.forename: Linda
authors.initials: L
authors.lastname: Beckers
authors.forename: Erwin
authors.initials: E
authors.lastname: Wijnands
authors.forename: Tom
authors.initials: T
authors.lastname: Seijkens
authors.forename: Dirk
authors.initials: D
authors.lastname: Lievens
authors.forename: Maik
authors.initials: M
authors.lastname: Drechsler
authors.forename: Norbert
authors.initials: N
authors.lastname: Gerdes
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
authors.forename: Radu V
authors.initials: RV
authors.lastname: Stan
authors.forename: Erik A L
authors.initials: EA
authors.lastname: Biessen
authors.forename: Esther
authors.initials: E
authors.lastname: Lutgens
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D001158:Arteries / Q000276:immunology; D050197:Atherosclerosis / Q000276:immunology* / Q000517:prevention & control; D051242:Caveolin 1 / Q000172:deficiency*; D005260:Female; D007249:Inflammation / Q000517:prevention & control; D007962:Leukocytes / Q000276:immunology; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D058226:Plaque, Atherosclerotic / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D051242:Caveolin 1; D019010:Vascular Cell Adhesion Molecule-1