ACTION OF TROPOELASTIN AND SYNTHETIC ELASTIN SEQUENCES ON VASCULAR TONE AND ON FREE CA2-CELLS( LEVEL IN HUMAN VASCULAR ENDOTHELIAL)

The elastic properties of extensible tissues such as arteries and skin are mainly due to the presence of elastic fibers whose major componen t is the extracellular matrix protein elastin. Pathophysiological degr adation of this protein leads to the generation of elastin peptides th at have been identified in the circulation in the mu g/mL to mu g/mL r ange. Similar concentrations of an elastin peptide preparation (kappa- elastin) were previously demonstrated to induce, among other biologica l actions, a dose-and endothelium-dependent vasorelaxation mediated by the elastin/laminin receptor and by endothelial NO production. To det ermine the elastin sequence(s) responsible for vasomotor activity and to learn more about possible signaling pathways, we have compared the action of different concentrations (10(-13) to 10(-7) mol/L) of recomb inant human tropoelastin, eight synthetic elastin peptides, and a cont rol peptide (VPVGGA) on both rat aortic ring tension and [Ca2+](i) of cultured human umbilical vein endothelial cells. No vasoactivity could be detected for VPVGGA and for the elastin-related sequences VGVGVA, PGVGVA, and GVGVA, Tropoelastin, VGV, PGV, and VGVAPG were found to in duce an endothelium-and dose-dependent vasorelaxation and to increase endothelial [Ca2+](i), whereas PVGV and VGVA produced these effects on ly at low concentration (10(-11) mol/L). A likely candidate for mediat ing the elastin peptide-related effects is the elastin/laminin recepto r, since the presence of lactose strongly inhibited the vasoactivity a ssociated with these compounds. Our results show that although the fla nking amino acids modulate its activity, VGV seems to be the core sequ ence recognized by the elastin receptor.