Inhibition of the angiogenesis by the MCP-1 (monocyte chemoattractant protein-1) binding peptide

• Published in: FEBS letters Vol. 579; no. 7; pp. 1597 - 1601
• Main Authors: Kim, Mee Young, Byeon, Cheol Woo, Hong, Kyung Hee, Han, Ki Hoon, Jeong, Sunjoo
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 14.03.2005
• Subjects: Angiogenesis; Angiogenesis Inhibitors - chemical synthesis; Angiogenesis Inhibitors - pharmacology; Animals; Aorta - drug effects; Biological Assay; Chemokine; Chemokine CCL2 - antagonists & inhibitors; Chemokine CCL2 - physiology; Chemokine receptor 2; Chemokine receptor 3; Humans; Monocyte chemoattractant protein-1; Neovascularization, Physiologic - drug effects; Oligopeptides - chemical synthesis; Oligopeptides - pharmacology; Peptide; Peptide Library; Rats; Receptors, CCR2; Receptors, Chemokine - drug effects; Receptors, Chemokine - physiology; Surface Plasmon Resonance; Chemokine; Monocyte chemoattractant protein-1; Angiogenesis; Chemokine receptor 2; Chemokine receptor 3; Peptide
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2005.01.070

The CC chemokine, monocyte chemoattractant protein-1 (MCP-1), plays a crucial role in the initiation of atherosclerosis and has direct effects that promote angiogenesis. To develop a specific inhibitor for MCP-1-induced angiogenesis, we performed in vitro selection employing phage display random peptide libraries. Most of the selected peptides were found to be homologous to the second extracellular loops of CCR2 and CCR3. We synthesized the peptide encoding the homologous sequences of the receptors and tested its effect on the MCP-1 induced angiogenesis. Surface plasmon resonance measurements demonstrated specific binding of the peptide to MCP-1 but not to the other homologous protein, MCP-3. Flow cytometry revealed that the peptide inhibited the MCP-1 binding to THP-1 monocytes. Moreover, CAM and rat aortic ring assays showed that the peptide inhibited MCP-1 induced angiogenesis. Our observations indicate that the MCP-1-binding peptide exerts its anti-angiogenic effect by interfering with the interaction between MCP-1 and its receptor.