Caveolin-1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T-cell response

David Engel*, Linda Beckers, Erwin Wijnands, Tom Seijkens, Dirk Lievens, Maik Drechsler, Norbert Gerdes, Oliver Soehnlein, Mat J.A.P. Daemen, Radu V. Stan, Erik A. L. Biessen, Esther Lutgens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Web of Science)

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.-Engel, D., Beckers, L., Wijnands, E., Seijkens, T., Lievens, D., Drechsler, M., Gerdes, N., Soehnlein, O., Daemen, M. J. A. P., Stan, R. V., Biessen, E. A. L., Lutgens, E. Caveolin-1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T-cell response. FASEB J. 25, 3838-3848 (2011). www.fasebj.org
Original languageEnglish
Pages (from-to)3838-3848
JournalFaseb Journal
Volume25
Issue number11
DOIs
Publication statusPublished - Nov 2011

Keywords

  • cholesterol
  • lipoproteins
  • endothelial cells
  • hematopoietic and nonhematopoietic compartment

Cite this