RESUMO
The angiogenic action of thrombin has been shown to be mediated by activation of the thrombin receptor. In this report we studied the effects of SFLLR, an agonist of the activated thrombin receptor and thrombin receptor peptide and non peptide antagonists on angiogenesis in the chick chorioallantoic membrane (CAM) system. As antagonists were used the tripeptide FPR and non-peptide 1,4-disubstituted piperazine derivatives. The pentapeptide SFLLR, like thrombin, caused a marked stimulation of angiogenesis in the CAM. FPR and the piperazine derivatives caused suppression of angiogenesis and in combination with thrombin antagonized its angiogenic effect. Thrombin and SFLLR activated progelatinase A (MMP-2) in the culture medium of human umbilical cord endothelial cells (HUVECs). MMP-2 is involved in the early steps of angiogenesis leading to local dissolution of basement membrane collagen and migration of the activated endothelial cells. FPR and the piperazine derivatives inhibited the activation of this enzyme. They also antagonised the effects of both thrombin and SFLLR on MMP-2 activation. These results suggest that non-thrombogenic agonists or antagonists of the activated thrombin receptor can be used as modulators of angiogenesis.
