Background Higher levels of C-reactive protein (CRP) predict cardiovascular events and also portend a poorer prognosis in patients with acute coronary syndromes. Much in-vitro and in-vivo data support a role for CRP in atherogenesis. Methods Using the one-bead-one-compound (OBOC) combinatorial library method we have successfully identified peptides against human CRP that inhibit its biological effects in-vitro. Hence we tested the effect of the best characterized inhibitor (CRP-i2) on the effects of CRP in an appropriate animal model, Wistar rats. Results Treatment with CRP resulted in significant increase in superoxide anion, nuclear factor kappaB (NFκb) activity and the release of biomarkers of inflammation from macrophages compared to Wistar rats treated with human albumin (HuSA). Pre-treatment with the inhibitor, CRP-i2, resulted in a significant reduction in CRP induced superoxide anion, NFκb activity and biomarkers of inflammation. Also, there were no observed clinical or laboratory related adverse effects. Conclusions We demonstrate that our novel peptide inhibitor attenuates the proinflammatory effects of CRP in-vivo. Future studies will examine the long-term effects of this inhibitor on vascular pathobiology.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine