Inhibition of the angiogenesis by the MCP-1 (monocyte chemoattractant protein-1) binding peptide.
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.
Kim
Mee Young
MY
Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Hannam-dong san 8, Yongsan-ku, Seoul 140-714, Republic of Korea.
Byeon
Cheol Woo
CW
Hong
Kyung Hee
KH
Han
Ki Hoon
KH
Jeong
Sunjoo
S
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001681:Biological Assay; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D019151:Peptide Library; D051381:Rats; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000187:drug effects / Q000502:physiology; D020349:Surface Plasmon Resonance
D020533:Angiogenesis Inhibitors; D018932:Chemokine CCL2; D009842:Oligopeptides; D019151:Peptide Library; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; C499860:histidyl-seryl-tryptophyl-arginyl-histidyl-phenylalanyl-histidyl-threonyl-leucyl-glycyl-glycyl-glycine