Background: Atherosclerosis is based on a chronic inflammatory process including the innate and adaptive immune response. Costimulatory molecules and their receptors provide decisive signals for antigen-specific cell activation. The contribution of B7-related pathways to atherosclerosis has hardly been explored.
Methods: In the present study, we investigated the contribution of B7-1 to inflammation and tissue injury in the human plaque microenvironment in order to identify possible target structures of future therapeutic agents ex vivo and in vitro.
Results: Carotid artery plaque stimulation with lipopolysaccharides (LPS) could be significantly inhibited by RhuDex(®), a specific inhibitor of the costimulatory molecule B7-1 ex vivo (P<0.001). Coculture of antigen-presenting cells with T-cells demonstrated that the inhibitory effects of RhuDex(®) derived from reduced T-cell activation. In addition, incubation of monocytes/macrophages with LPS and RhuDex(®) resulted in an inhibitory negative feedback on antigen-presenting cells. Signaling pathways affected by RhuDex(®) seem to be nuclear transcription factor kappa B, activator protein-1, and extracellular signal-regulated kinase 1/2.
Conclusion: The present data support B7-1 alone as an important costimulatory molecule in the context of LPS-mediated inflammation in atherosclerotic lesions. Due to its marked inhibitory effects, RhuDex(®) may be a useful therapy to modulate the inflammatory milieu in atherosclerosis.
Keywords: B7; CD86; atherosclerosis; costimulation.