title: A CD31-derived peptide prevents angiotensin II-induced atherosclerosis progression and aneurysm formation.
abstract: OBJECTIVE
  The loss of the inhibitory receptor CD31 on peripheral T lymphocytes is associated with the incidence of atherosclerotic complications such as abdominal aortic aneurysms (AAA) in patients and plaque thrombosis in mice. However, we have recently discovered that a small fragment of extracellular CD31 remains expressed on the surface of the apparently 'CD31-negative' T-cells and that it is possible to restore the CD31-mediated T-cell inhibition in vivo by using a synthetic CD31-derived peptide. Here, we wanted to evaluate the therapeutic potential of the peptide in an experimental model of accelerated atherosclerosis and AAA formation.
  
  
  RESULTS
  The effect of the murine CD31-derived peptide (aa 551-574, 1.5 mg/kg/day, sc) was evaluated on the extent of atherosclerotic plaques and the incidence of AAA in 28-week-old apolipoprotein E knockout mice (male, n ≥ 8/group) submitted to chronic angiotensin II infusion. The therapeutic mechanisms of the peptide were assessed by evaluating its effect on immune cell functions in vivo and in vitro. The prevalence of angiotensin II-induced AAA correlated with the loss of extracellular CD31 on T-cells. CD31 peptide treatment reduced both aneurysm formation and plaque size (P < 0.05 vs. control). Protection was associated with reduced perivascular leucocyte infiltration and T-cell activation in vivo. Functional in vitro studies showed that the peptide is able to suppress both T-cell and macrophage activation.
  
  
  CONCLUSIONS
  CD31 peptides could represent a new class of drugs intended to prevent the inflammatory cell processes, such as those underlying progression of atherosclerosis and development of AAA.
authors.affiliation: INSERM, UMRS 698, 46 rue Henri Huchard, F-75018 Paris,  France.
authors.forename: Giulia
authors.initials: G
authors.lastname: Fornasa
authors.forename: Marc
authors.initials: M
authors.lastname: Clement
authors.forename: Emilie
authors.initials: E
authors.lastname: Groyer
authors.forename: Anh-Thu
authors.initials: AT
authors.lastname: Gaston
authors.forename: Jamila
authors.initials: J
authors.lastname: Khallou-Laschet
authors.forename: Marion
authors.initials: M
authors.lastname: Morvan
authors.forename: Kevin
authors.initials: K
authors.lastname: Guedj
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: Alain
authors.initials: A
authors.lastname: Tedgui
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Antonino
authors.initials: A
authors.lastname: Nicoletti
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Caligiuri
mesh_terms: D000804:Angiotensin II; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001018:Aortic Diseases / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000494:pharmacology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D001057:Apolipoproteins E; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011948:Receptors, Antigen, T-Cell; D000804:Angiotensin II