Inhibition of TRAP-induced angiogenesis by the tripeptide Phe-Pro-Arg, a thrombin-receptor-derived peptide analogue

✍ Scribed by Michael E. Maragoudakis; Eva Pipili-Synetos; Eleni Sakkoula; Dimitris Panagiotopoulos; Nancy Craniti; John M. Matsoukas

• Book ID: 104632891
• Publisher: Springer Netherlands
• Year: 1996
• Tongue: English
• Weight: 413 KB
• Volume: 3
• Category: Article
• ISSN: 1573-3149
• DOI: 10.1007/bf00128112

✦ Synopsis

We have recently shown that thrombin promotes angiogenesis by a mechanism independent of fibrin formation. In the present paper, we investigated the effect of the thrombin-receptor-activating tetradecapeptide (TRAPH4, S42FLLRNPNDKYEPFss ) for its effects on angiogenesis in the chick chorioallantoic membrane (CAM) system of angiogenesis. A dose-dependent promotion of angiogenesis is evident with TRAP. In contrast, a thrombin-receptorderived tripeptide analogue H-Phe-Pro-Arg-OH (FPR), which was designed based on the S42FLLR46 sequence, caused an inhibition of angiogenesis in the CAM, and when it was combined with TRAP it caused a complete reversal of the angiogenesis-promoting effect of TRAP. These results indicate that the proteolytic exposure of the receptor N-terminal tetradecapeptide by thrombin can activate the post-thrombotic events related to angiogenesis. These events can be modulated by constrained peptide analogues such as FPR.