Urotensin-II-stimulated expression of pro-angiogenic factors in human vascular endothelial cells.

Urotensin-II (U-II) is an endogenous peptide recently characterized as a "nonclassic" pro-angiogenic cytokine. In fact, human vascular endothelial cells express the U-II receptor and exhibit a strong in vitro angiogenic response to the peptide, which was specifically triggered by the binding of U-II to its receptor and involved the activation of ERK1/2 and PI3K/Akt signaling pathways. Moreover, available studies, designed to investigate the pro-angiogenic effect quite shortly following U-II stimulation, suggested that the angiogenic action of the peptide was direct and not associated with an increased expression of vascular endothelial growth factor (VEGF) and/or its receptors.

Synthesis, in vitro and in vivo preliminary evaluation of anti-angiogenic properties of some pyrroloazaflavones.

This work investigated the in vitro and in vivo anti-angiogenic activity of some pyrroloazaflavones, exactly 2-phenyl-1H-pyrrolo[2,3-h]quinolin-4(7H)ones, with vinblastine as reference compound. Growth inhibitory activity, migration, and capillary-like structures formation were determined in human umbilical vein endothelial cell cultures, and Matrigel plug assay was carried out to evaluate in vivo effects on angiogenesis. Collectively, our results indicate that some pyrroloazaflavone derivatives, at non-cytotoxic concentrations and like vinblastine are able: (i) to exert in vitro anti-angiogenic activity and (ii) to counteract in vitro and in vivo the pro-angiogenic effects of fibroblast growth factor-2 (FGF-2).

Involvement of vascular endothelial growth factor signaling in CLR/RAMP1 and CLR/RAMP2-mediated pro-angiogenic effect of intermedin on human vascular endothelial cells.

Intermedin (IMD) is a recently discovered peptide closely related to adrenomedullin. Its principal physiological activity is its role in the regulation of the cardiovascular system, where it exerts a potent hypotensive effect. In addition, data were recently provided showing that this peptide is able to exert a clearcut pro-angiogenic effect both in vitro and in vivo.

The pro-angiogenic activity of urotensin-II on human vascular endothelial cells involves ERK1/2 and PI3K signaling pathways.

Human vascular endothelial cells express the urotensin-II (U-II) receptor and exhibit a strong in vitro angiogenic response to the peptide. Thus, in the present study an in vitro model, based on human umbilical vein endothelial cells (HUVEC) cultured on Matrigel, was used to characterize more in detail the signaling pathways that control the pro-angiogenic action of U-II. The activation of the U-II receptor (UT) was associated with an increase of intracellular calcium concentration.