083 - Th1 cytokines as proatherogenic key players of atherosclerotic plaque progression (ID 934)
Abstract
Background and Aims
Although a Th1-biased immune response has been shown to accelerate atherosclerosis, the involvement of Th1-specific cytokines in plaque destabilization is not completely elucidated. In our study, we characterized the peripheral Th1 response, based on cytokine profile, in different stages of atherogenesis.
Methods
Carotid specimens and blood was collected from patients undergoing endarterectomy. Histological analyses of plaque cross-sections served for classification into stable and vulnerable plaques, while different T cell subsets were quantified in blood by FACS analyses. Serum concentration of cytokines were measured by luminex technology. As an in vitro model for the initial stage of atherogenesis, human endothelial cells were seeded into bifurcation-flow-through-slides and stimulated with Th1 cytokines for different incubation times, whereupon perfusion with THP-1 monocytes under flow served to assess cell adhesion.
Results
Patients with vulnerable plaques had higher IL-18 serum concentrations and a trend towards increased TNF-a levels compared to those with stable plaques. Additionally, the vulnerable plaque phenotype was associated with increased frequencies of Th1 cells and cytotoxic T cells in blood. In the applied in vitro model, both, IL-18 and TNF-a induced an enhanced THP-1 cell adhesion to the endothelial monolayer. However, IL-18 needed longer incubation times than TNF-a to enhance cell adhesion.
Conclusions
Amongst the analyzed Th1 cytokines, especially TNF-a and IL-18 seem to be involved in different stages of plaque progression. In patients, high serum IL-18 was associated with increased plaque vulnerability. In vitro, both Th1 cytokines induce cell adhesion to endothelium, suggesting an important role also in endothelial dysfunction.
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