Genetic deletion or antibody blockade of α1β1 integrin induces a stable plaque phenotype in ApoE-/- mice

Kitty Schapira, Esther Lutgens, Antonin De Fougerolles, Andrew Sprague, Anouk Roemen, Humphrey Gardner, Victor Koteliansky, Mat Daemen, Sylvia Heeneman

Research output: Contribution to journalArticlepeer-review


Objective - Adhesive interactions between cells and the extracellular matrix play an important role in inflammatory diseases like atherosclerosis. We investigated the role of the collagen-binding integrin α1β1 in atherosclerosis. Methods and Results - ApoE-/- mice were α1-deficient or received early or delayed anti-α1 antibody treatment. Deficiency in α1 integrin reduced the area of atherosclerotic plaques and altered plaque composition by reducing inflammation and increasing extracellular matrix. In advanced plaques, α1-deficient mice had a reduced macrophage and CD3+ cell content, collagen and smooth muscle cell content increased, lipid core sizes decreased, and cartilaginous metaplasia occurred. Anti-α1 antibody treatment reduced the macrophage content in initial plaques after early and delayed treatment, decreased the CD3+ cell content in advanced plaques after delayed treatment, and increased the collagen content in initial and advanced plaques after delayed treatment. Migration assays performed on α1-deficient macrophages on collagen I and IV substrata revealed that α1-deficient cells can migrate on collagen I, but not IV. Anti-α1 antibody treatment of ApoE-/- macrophages also inhibited migration of cells on collagen IV. Conclusions - Our results suggest that α1β1 integrin is involved in atherosclerosis by mediating the migration of leukocytes to lesions by adhesion to collagen IV. Blocking this integrin reduces atherosclerosis and induces a stable plaque phenotype.

Original languageEnglish (US)
Pages (from-to)1917-1924
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number9
StatePublished - Sep 2005


  • Atherosclerosis
  • Collagen
  • Extracellular matrix
  • Integrin
  • Macrophages

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Genetic deletion or antibody blockade of α1β1 integrin induces a stable plaque phenotype in ApoE-/- mice'. Together they form a unique fingerprint.

Cite this