title: Synthetic peptide fragment (65-76) of monocyte chemotactic protein-1 (MCP-1) inhibits MCP-1 binding to heparin and possesses anti-inflammatory activity in stable angina patients after coronary stenting.
abstract: OBJECTIVE
  The peptide from C-terminal domain of MCP-1 (Ingramon) has been shown to inhibit monocyte migration and possess anti-inflammatory activity in animal models of inflammation and post-angioplasty restenosis. Here, we investigate the effect of Ingramon treatment on blood levels of acute-phase reactants and chemokines in patients after coronary stenting and the mechanisms of Ingramon anti-inflammatory activity.
  
  
  METHODS
  Eighty-seven patients with ischemic heart disease (IHD) who faced the necessity of coronary angiography (CA) were enrolled. In 67 patients, one-stage coronary stenting was performed; 33 of them were treated with Ingramon in addition to standard therapy. Twenty patients underwent CA only.
  
  
  METHODS
  High-sensitivity C-reactive protein (hsCRP) and fibrinogen blood levels were detected routinely. The chemokine concentration in plasma was measured by enzyme-linked immunosorbent assay (ELISA) or cytometric bead array-based immunoassay. Intracellular Ca(2+) levels and cell surface integrin exposure were assayed by flow cytometry. MCP-1 dimerization was studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). MCP-1-heparin binding was assessed with a biosensor and ELISA.
  
  
  CONCLUSIONS
  Ingramon treatment was accompanied by less pronounced elevation of hsCRP and fibrinogen levels and decreased MCP-1 concentration in plasma in patients after coronary stenting. Ingramon had no effect on MCP-1 interaction with cell receptors or MCP-1 dimerization, but inhibited MCP-1 binding to heparin. The anti-inflammatory activity of the peptide may be mediated by an impaired chemokine interaction with glycosaminoglycans.
authors: Institute of Experimental Cardiology, Russian Cardiology Research and Production Complex of Ministry of Health RF, 3rd Cherepkovskaya str., 15, Moscow 121552, Russia. arefieva@cardio.ru
authors: T I
authors: TI
authors: Arefieva
authors: T L
authors: TL
authors: Krasnikova
authors: A V
authors: AV
authors: Potekhina
authors: N U
authors: NU
authors: Ruleva
authors: P I
authors: PI
authors: Nikitin
authors: T I
authors: TI
authors: Ksenevich
authors: B G
authors: BG
authors: Gorshkov
authors: M V
authors: MV
authors: Sidorova
authors: Zh D
authors: ZhD
authors: Bespalova
authors: N B
authors: NB
authors: Kukhtina
authors: S I
authors: SI
authors: Provatorov
authors: E A
authors: EA
authors: Noeva
authors: E I
authors: EI
authors: Chazov
mesh_terms: D000210:Acute-Phase Reaction; D000368:Aged; D000787:Angina Pectoris / Q000473:pathology*; D017130:Angioplasty; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism*; D017023:Coronary Angiography / Q000379:methods; D023903:Coronary Restenosis; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D017202:Myocardial Ischemia / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015607:Stents
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D010446:Peptide Fragments; C542772:ingramon; D005340:Fibrinogen; D006493:Heparin; D002097:C-Reactive Protein