Atheroprotective effect of CD31 receptor globulin through enrichment of circulating regulatory T-cells
E Groyer, A Nicoletti, H Ait-Oufella… - Journal of the American …, 2007 - jacc.org
E Groyer, A Nicoletti, H Ait-Oufella, J Khallou-Laschet, A Varthaman, AT Gaston, O Thaunat…
Journal of the American College of Cardiology, 2007•jacc.orgObjectives: 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 …
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 …
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.
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