A CD31-derived peptide prevents angiotensin II-induced atherosclerosis progression and aneurysm formation

Giulia Fornasa, Marc Clement, Emilie Groyer, Anh Thu Gaston, Jamila Khallou-Laschet, Marion Morvan, Kevin Guedj, Srini V. Kaveri, Alain Tedgui, Jean Baptiste Michel, Antonino Nicoletti, Giuseppina Caligiuri

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: 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. Methods and results: The effect of the murine CD31-derived peptide (aa 551574, 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. Conclusion: 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. Published on behalf of the European Society of Cardiology. All rights reserved.

Original languageEnglish
Pages (from-to)30-37
Number of pages8
JournalCardiovascular Research
Volume94
Issue number1
DOIs
Publication statusPublished - Apr 1 2012

Keywords

  • Aneurysm
  • Angiotensin II
  • Atherosclerosis
  • CD31
  • Peptides

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

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