Background and Aims

Increased amount of glycosylation on T cells surface results in the augmented immune response. Our aim was to profile immune cells glycans signature during atherosclerosis.

Methods

Sialic acid (SIA) and mannose expression on the surface of T cells and monocytes from blood of LDL-R KO mice fed with chow or WTD for 8 weeks and FH patients was analysed by flow cytometry via WGA (Sialic acid and N-acetyl-D-glucosamine) and ConA (mannose) lectin binding to immune cells.

Results

In parallel with increase cholesterolaemia in WTD fed LDL-R KO mice compared to chow (635.7±36.77mg/dL;199.9±13.73mg/dL), circulating lymphocytes and monocytes from LDL-R KO mice fed with WTD presented increased expression of SIA compared to chow fed mice (1.88±0.14-fold for CD4⁺, 1.78±0.51-fold for CD8⁺, 2.03±0.1-fold* for Ly6c^Low and 1.78±0.4-fold for Ly6c^Highcells). Viceversa, changes in mannose expression are not significant (0.83±0.04-fold for CD4⁺, 0.79±0.04-fold for CD8⁺, 0.87±0.05-fold for Ly6c^Low and 0.76±0.05-fold for Ly6c^High cells. (*p<0.05).

In line with these findings, circulating cells from FH patients presented increased SIA levels (5.44±0.83-fold** for CD4⁺, 4±0.32-fold** for CD8⁺, 2.95±0.13-fold** for CD14⁺ and 2.76±0.1-fold** for CD16⁺) compared to controls, while no differences were observed in the amount of mannose (1.15±0.05-fold for CD4⁺, 1.21±0.14-fold for CD8⁺, 1.28±0.06-fold for CD14⁺, 0.21±0.22-fold for CD16⁺). (**p<0.01).

Conclusions

Our data indicate that hypercholesterolaemia impacts glycans signature on circulating immune cells in humans and in experimental models. Whether the increased SIA/mannose ratio observed in hypercholesterolaemic conditions could mark a setting associated with augmented immune cells activation during atherosclerosis is under investigation.