Action of Tropoelastin and Synthetic Elastin Sequences on Vascular Tone and on Free Ca²⁺ Level in Human Vascular Endothelial Cells

From the Groupe d'Electrophysiologie Moléculaire (G.F., S.G., J.V.), Laboratoire de Bioénergétique Fondamentale et Appliquée, Université Joseph Fourier, Grenoble, France; the Department of Biochemistry (A.S.W.), University of Sydney, New South Wales, Australia; the Laboratoire de Biochimie Analytique et Synthèse Bioorganique (J.W.), Université Claude Bernard, Villeurbanne, France; the Centre de Recherche en Gérontologie et Gériatrie (T.F.), Hopital d'Youville, Université de Sherbrooke, Québec, Canada; INSERM U460 (M.-P.J.), Paris, France; the Department of Cell Biology and Physiology (R.P.M.), Washington University School of Medicine, St Louis, Mo; and the Laboratoire de Biologie du Vieillissement (L.R.), CHU Pitié et Recherche Ophtalmologique, Hotel-Dieu, Université Paris 6, Paris, France.

Correspondence to Gilles P. Faury, PhD, Department of Cell Biology and Physiology, Washington University, School of Medicine, Campus Box 8228, 660 S Euclid Ave, St Louis, MO 63110. E-mail gfaury{at}cellbio.wustl.edu

Abstract—The elastic properties of extensible tissues such as arteries and skin are mainly due to the presence of elastic fibers whose major component is the extracellular matrix protein elastin. Pathophysiological degradation of this protein leads to the generation of elastin peptides that have been identified in the circulation in the ng/mL to µg/mL range. Similar concentrations of an elastin peptide preparation (-elastin) were previously demonstrated to induce, among other biological actions, a dose- and endothelium-dependent vasorelaxation mediated by the elastin/laminin receptor and by endothelial NO production. To determine 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 recombinant human tropoelastin, eight synthetic elastin peptides, and a control 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 induce an endothelium- and dose-dependent vasorelaxation and to increase endothelial [Ca²⁺]_i, whereas PVGV and VGVA produced these effects only at low concentration (10^-11 mol/L). A likely candidate for mediating the elastin peptide–related effects is the elastin/laminin receptor, since the presence of lactose strongly inhibited the vasoactivity associated with these compounds. Our results show that although the flanking amino acids modulate its activity, VGV seems to be the core sequence recognized by the elastin receptor.

Key Words: elastin • elastin/laminin receptor • vascular tone • endothelial cell • [Ca²⁺]_i

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