首页> 外文期刊>Endothelium: Journal of endothelial cell research >Modulation of angiogenesis and progelatinase a by thrombin receptor mimetics and antagonists.
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Modulation of angiogenesis and progelatinase a by thrombin receptor mimetics and antagonists.

机译:凝血酶受体模拟物和拮抗剂对血管生成和明胶酶α的调节。

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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.
机译:凝血酶的血管生成作用已被证明是由凝血酶受体的激活介导的。在本报告中,我们研究了活化的凝血酶受体,凝血酶受体肽和非肽拮抗剂的激动剂SFLLR对鸡绒膜尿囊膜(CAM)系统中血管生成的影响。作为拮抗剂,使用三肽FPR和非肽的1,4-二取代的哌嗪衍生物。五肽SFLLR与凝血酶一样,在CAM中引起明显的血管生成刺激。 FPR和哌嗪衍生物引起血管生成的抑制,并与凝血酶联合拮抗其血管生成作用。凝血酶和SFLLR在人脐带内皮细胞(HUVEC)的培养基中激活了明胶酶A(MMP-2)。 MMP-2参与血管生成的早期步骤,导致基底膜胶原的局部溶解和活化的内皮细胞的迁移。 FPR和哌嗪衍生物抑制了该酶的活化。他们还拮抗了凝血酶和SFLLR对MMP-2激活的影响。这些结果表明,活化的凝血酶受体的非血栓形成性激动剂或拮抗剂可以用作血管生成的调节剂。

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