260 - Effects of evolocumab on immune cells activation in human atherosclerotic plaques (ID 789)
Abstract
Background and Aims
Evolocumab, an anti-PCSK9 antibody, is used to reduce LDL-cholesterol level in patients with cardiovascular diseases. At the same time, it was found, that PCSK9 itself is involved not only in lipids metabolism but also in inflammatory process. The aim of our study was to investigate the effects of the evolocumab treatment on T-cell activation in human atherosclerotic plaques.
Methods
We collected 20 atherosclerotic plaques from patients undergoing carotid endarterectomy. For culture of atherosclerotic plaques’ explants we used an original ex vivo method, which was tested previously. During culture atherosclerotic plaques’ explants were treated with evolocumab in concentration 11 μg/ml, which was selected using cell culture experiments as a maximal concentration without a cytotoxic effect. After 13 days of culture we performed enzymatic digestion of plaque explants and measured markers of activation of T cells derived from plaques by means of flow cytometry.
Results
We found that atherosclerotic plaques’ explants treated with evolocumab for 13 days compared to control have a significantly decreased CD25+ expression (20[5.6;23,3]% vs 27.2[20.2;37,2]%, respectively, p<0.05) and CD25+CD38+ co-expression (2.4[0.9;6.1]% vs 4.4[1.4;9.3]% of, respectively, p<0.05) on CD8 T cells. They also showed a trend towards decreased CD25+ expression (15.9[11.4;21.5]% vs 18.2[14.7;24,9]% respectively, p=0.098) and CD25+CD38+ co-expression (2.3[1.6;5.7]% vs 3.9[1.8;6.7]%, respectively, p=0.093) on CD4 T cells.
Conclusions
Evolocumab treatment for 13 days decreased activation of T-cells in atherosclerotic plaque during ex vivo culture. These results may bring an additional explanation to the profound impact of anti-PCSK9 antibodies therapy on prognosis of patients with cardiovascular diseases.
*This work was sponsored by Amgen agreement #20177269
