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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.

AbstractOBJECTIVE AND DESIGN:
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.
SUBJECTS:
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.
RESULTS AND 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.
AuthorsT I Arefieva, T L Krasnikova, A V Potekhina, N U Ruleva, P I Nikitin, T I Ksenevich, B G Gorshkov, M V Sidorova, Zh D Bespalova, N B Kukhtina, S I Provatorov, E A Noeva, E I Chazov
JournalInflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 60 Issue 10 Pg. 955-64 (Oct 2011) ISSN: 1420-908X [Electronic] Switzerland
PMID21744268 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents
  • Chemokine CCL2
  • Peptide Fragments
  • ingramon
  • Fibrinogen
  • Heparin
  • C-Reactive Protein
Topics
  • Acute-Phase Reaction
  • Aged
  • Angina Pectoris (pathology)
  • Angioplasty
  • Anti-Inflammatory Agents (pharmacology)
  • C-Reactive Protein (metabolism)
  • Chemokine CCL2 (metabolism)
  • Coronary Angiography (methods)
  • Coronary Restenosis
  • Female
  • Fibrinogen (metabolism)
  • Heparin (metabolism)
  • Humans
  • Male
  • Middle Aged
  • Monocytes (cytology)
  • Myocardial Ischemia (pathology)
  • Peptide Fragments (pharmacology)
  • Protein Binding
  • Protein Structure, Tertiary
  • Stents

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