PMID- 17612642
OWN - NLM
STAT- MEDLINE
DCOM- 20071016
LR  - 20070706
IS  - 0008-4212 (Print)
IS  - 0008-4212 (Linking)
VI  - 85
IP  - 3-4
DP  - 2007 Mar-Apr
TI  - The peptide analogue of MCP-1 65-76 sequence is an inhibitor of inflammation.
PG  - 332-40
AB  - 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 by 1H-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 with 99mTc 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.
FAU - Chazov, Evgeny I
AU  - Chazov EI
AD  - Russian Cardiology Research Complex, 3 Cherepkovskaya, 15a, Moscow 121552 Russia.
FAU - Bespalova, Janna D
AU  - Bespalova JD
FAU - Arefieva, Tatiana I
AU  - Arefieva TI
FAU - Kukhtina, Nadezhda B
AU  - Kukhtina NB
FAU - Sidorova, Maria V
AU  - Sidorova MV
FAU - Provatorov, Sergey I
AU  - Provatorov SI
FAU - Krasnikova, Tatiana L
AU  - Krasnikova TL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Canada
TA  - Can J Physiol Pharmacol
JT  - Canadian journal of physiology and pharmacology
JID - 0372712
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Angina Pectoris/blood
MH  - Angina, Unstable/blood
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Cell Line
MH  - Chemokine CCL2/blood/*chemistry
MH  - Chemotaxis/drug effects
MH  - Humans
MH  - Inflammation/chemically induced/*drug therapy/pathology
MH  - Leukocytes/drug effects/immunology
MH  - Lipopolysaccharides
MH  - Macaca fascicularis
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Peptide Fragments/*therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Skin/pathology
EDAT- 2007/07/07 09:00
MHDA- 2007/10/17 09:00
CRDT- 2007/07/07 09:00
PHST- 2007/07/07 09:00 [pubmed]
PHST- 2007/10/17 09:00 [medline]
PHST- 2007/07/07 09:00 [entrez]
AID - y07-008 [pii]
AID - 10.1139/y07-008 [doi]
PST - ppublish
SO  - Can J Physiol Pharmacol. 2007 Mar-Apr;85(3-4):332-40. doi: 10.1139/y07-008.