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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

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Abstract

Objective 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 Ca2+ 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.

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Acknowledgments

The study was supported by Russian Basic Research Foundation projects 09-04-00545, 10-04-00015, 11-02-01440, by GC N 16.512.11.2124, and by Moscow Government, Scientific and Technical Programme “Development of new methods of prevention, diagnosis and treatment of atherosclerosis and its complications” for 2009-2011, contract number 8/3-280n-10.

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Authors and Affiliations

  1. Institute of Experimental Cardiology, Russian Cardiology Research and Production Complex of Ministry of Health RF, 3rd Cherepkovskaya str., 15, Moscow, 121552, Russia

    T. I. Arefieva, T. L. Krasnikova, N. U. Ruleva, M. V. Sidorova, Zh. D. Bespalova & N. B. Kukhtina

  2. Institute of Clinical Cardiology, Russian Cardiology Research and Production Complex of Ministry of Health RF, 3rd Cherepkovskaya str., 15, Moscow, 121552, Russia

    A. V. Potekhina, S. I. Provatorov & E. A. Noeva

  3. General Physics Institute of Russian Academy of Sciences, Vavilov str., 38, Moscow, 119991, Russia

    P. I. Nikitin, T. I. Ksenevich & B. G. Gorshkov

  4. Russian Cardiology Research and Production Complex of Ministry of Health RF, 3rd Cherepkovskaya str., 15, Moscow, 121552, Russia

    E. I. Chazov

Authors
  1. T. I. Arefieva
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  2. T. L. Krasnikova
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  3. A. V. Potekhina
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  4. N. U. Ruleva
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  5. P. I. Nikitin
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  6. T. I. Ksenevich
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  7. B. G. Gorshkov
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  8. M. V. Sidorova
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  9. Zh. D. Bespalova
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  10. N. B. Kukhtina
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  11. S. I. Provatorov
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  12. E. A. Noeva
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  13. E. I. Chazov
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Corresponding authors

Correspondence to T. I. Arefieva or T. L. Krasnikova.

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Responsible Editor: Artur Bauhofer.

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Arefieva, T.I., Krasnikova, T.L., Potekhina, A.V. et al. 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. Inflamm. Res. 60, 955–964 (2011). https://doi.org/10.1007/s00011-011-0356-z

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  • DOI: https://doi.org/10.1007/s00011-011-0356-z

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