title: A novel peptide inhibitor attenuates C-reactive protein's pro-inflammatory effects in-vivo.
abstract: 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.
authors.affiliation: Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, CA, United States; Veterans Affairs Medical Center, Mather, CA, United States. Electronic address: ishwarlal.jialal@ucdmc.ucdavis.edu.
authors.forename: I
authors.initials: I
authors.lastname: Jialal
authors.forename: S
authors.initials: S
authors.lastname: Devaraj
authors.forename: G
authors.initials: G
authors.lastname: Smith
authors.forename: K S
authors.initials: KS
authors.lastname: Lam
authors.forename: P R
authors.initials: PR
authors.lastname: Kumaresan
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000517:prevention & control; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000097:blood*; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018836:Inflammation Mediators; D010446:Peptide Fragments; D002097:C-Reactive Protein
keywords: CRP; Inflammation; Macrophages