The peptide analogue of MCP-1 65–76 sequence is an inhibitor of inflammationThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute
| Autor: | T. L. Krasnikova, N. B. Kukhtina, Evgeny I. ChazovE.I. Chazov, Tatiana I. Arefieva, Maria Sidorova, Janna D. BespalovaJ.D. Bespalova, S I Provatorov |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 85:332-340 |
| ISSN: | 1205-7541 0008-4212 |
| Popis: | Inflammation plays an important role in vessel wall remodeling that occurs in atherosclerosis and postangioplasty restenosis. Monocytic chemoattractant protein-1 (MCP-1) is one of the main attractors of monocytes and some lymphocyte subsets to the damaged vessel. The aims of the study were to confirm MCP-1 participation in the development of acute coronary syndromes, to produce the potential MCP-1 peptide antagonist, and to investigate its effects in vitro and in vivo in different animal models of inflammation. MCP-1 plasma concentration was measured by ELISA (enzyme-linked immunosorbent assay). Chemokine receptor expression by cells isolated from human atherosclerotic lesions was assessed by direct immunofluorescence and flow cytometry. MCP-1 sequence was analyzed with Peptide Companion software and peptides were synthesized using Fmoc strategy. The peptide resistance to degradation was checked by1H-NMR spectroscopy. The peptide effect on MCP-1-stimulated cell migration was studied in Boyden chamber and in mouse air pouch model, and its influence on lipopolysaccharide (LPS)-induced inflammatory cell recruitment was investigated in models of subcutaneous inflammation in rats and nonhuman primates. We revealed nearly a 2-fold increase of MCP-1 plasma level in patients with unstable angina in comparison with patients with stable angina. The atherosclerotic plaque specimens obtained from patients with unstable angina contained a significant amount of chemokine receptor-expressing leukocytes. Peptide from MCP-1 C-terminal 65–76 sequence (peptide X) inhibited MCP-1-stimulated monocytic cell migration in vitro and in vivo. Peptide X labeled with99mTc accumulated specifically at sites of inflammation in rats. Peptide X administrated i.m and i.v. suppressed monocyte and granulocyte recruitment induced by subcutaneous injection of LPS in the back of rats and non-human primates. Our data demonstrate that MCP-1-mediated chemotaxis could be responsible for atherosclerotic plaque “destabilization”. Peptide X may represent a new class of anti-inflammatory drugs to be used in cardiology. |
| Databáze: | OpenAIRE |
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