Author + information
- Received November 30, 2006
- Revision received March 22, 2007
- Accepted April 3, 2007
- Published online July 24, 2007.
- Emilie Groyer, MSc⁎,
- Antonino Nicoletti, PhD⁎,
- Hafid Ait-Oufella, MD†,
- Jamila Khallou-Laschet, PhD⁎,
- Aditi Varthaman, MSc⁎,
- Anh-Thu Gaston, BSc⁎,
- Olivier Thaunat, MD⁎,
- Srini V. Kaveri, DVM, PhD⁎,
- Radek Blatny, MSc‡,
- Hannes Stockinger, PhD‡,
- Ziad Mallat, MD, PhD† and
- Giuseppina Caligiuri, MD, PhD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Giuseppina Caligiuri, INSERM UMR S 872, équipe 16, Les Cordeliers, 15, rue de l’Ecole de Médecine, Paris F-75006, France.
Objectives This study was designed to evaluate whether replacing CD31 (PECAM-1) signaling can restore the regulation of lymphocyte activation and improve experimental atherosclerosis.
Background Atherosclerosis, the principal cause of myocardial infarction and stroke, is due to the development of a pathogenic immune response within the vascular wall and is aggravated by the reduction of regulatory T-cells. CD31, a transmembrane adhesion molecule with inhibitory signaling functions, is physiologically expressed on blood and vascular resting cells but is lost in pathologic conditions associated with atherosclerosis.
Methods Replacement therapy with a CD31 receptor globulin (Rg) was delivered by in vivo gene transfer in 6-week-old apolipoprotein E knockout mice (n = 14 per group) every 5 weeks for 6 months. Control groups were treated with a truncated CD31Rg or with vehicle alone. At the end of the study, plaque size and morphology and blood T-cell compartment were analyzed in all mice.
Results Atherosclerotic lesions of CD31Rg-treated mice were smaller (p < 0.01) and showed less neovascularization and intraplaque hemorrhage (p < 0.05) compared with control subjects. Furthermore, circulating regulatory T-cells were increased in vivo (p < 0.01) and showed normal suppressive function on proliferation of conventional T-cells in vitro. Indeed, CD31Rg treatment led to blunted blood T-cell activation (p < 0.05) and reduced T-cell infiltration within plaques (p < 0.01).
Conclusions Our data suggest that CD31 plays a key role in the regulation of the immune response linked to atherosclerosis. CD31-targeting therapeutic approaches may therefore be envisaged for preventing and treating atherosclerotic diseases.
This work was supported in part by the “Fondation de France” (grant no. 2006005656) and the GEN-AU Program of the Austrian Federal Ministry of Education, Science, and Culture.
- Received November 30, 2006.
- Revision received March 22, 2007.
- Accepted April 3, 2007.
- American College of Cardiology Foundation