The leukocyte-shed short form of plasma soluble CD31 identifies coronary artery disease in patients at low risk: insights from the "Capire" study

Background and Aims CD31 is cleaved at the surface of activated leukocytes, yielding a short soluble (s)CD31 form that circulates together with the long one, physiologically produced by endothelial cells. In pathologic vascular conditions, the decreased production of the long form may be in balance with the release of the leukocyte-shed short form, puzzling the biological significance of total sCD31 measures in plasma. In order to evaluate the independent putative role of activation-driven leukocyte CD31 shedding in the pathogenesis of Coronary Atherosclerosis Disease (CAD), we measured the two forms in the plasma of stable patients with a low risk factor burden (0 to 1 risk factor, excluded diabetes) and without previous diagnosis of CAD, enrolled in the study CAPIRE (Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation). Methods The long and short forms of sCD31 were measured using epitope-mapped monoclonal antibodies and a bead-based multicolor method, as described in doi: 10.4049/jimmunol.0902219. Patients were distributed in two groups, “CAD” (> 5 segments involvement detected by coronary computed tomography angiography, n = 234) and “noCAD” (no plaque detected, n = 88). Data were adjusted for inflammatory covariates (plasma hsCRP and IL-6 levels) prior to statistical analysis. Results The relative fraction of leukocyte-shed short sCD31 form was significantly augmented in CAD patients (P  Fig. 1 ) whereas total (short + long form) sCD31 plasma levels were similar in all patients (32 ± 27 vs. 31 ± 43 ng/ml, NS, not shown). Conclusions Leukocyte activation, revealed by the increased proportion of the short sCD31, is significantly increased in patients affected by CAD in wpite of a very low “classical” risk burden, suggesting a pcausal role in the pathogenesis of human atherosclerosis.