title: ADAM-17 regulates endothelial cell morphology, proliferation, and in vitro angiogenesis.
abstract: Modulation of angiogenesis is a promising approach for treating a wide variety of human diseases including ischemic heart disease and cancer. In this study, we show that ADAM-17 is an important regulator of several key steps during angiogenesis. Knocking down ADAM-17 expression using lentivirus-delivered siRNA in HUVECs inhibited cell proliferation and the ability of cells to form close contact in two-dimensional cultures. Similarly, ADAM-17 depletion inhibited the ability of HUVECs to form capillary-like networks on top of three-dimensional Matrigel as well as in co-culture with fibroblasts within a three-dimensional scaffold. In mechanistic studies, both baseline and VEGF-induced MMP-2 activation and Matrigel invasion were inhibited by ADAM-17 depletion. Based on our findings we propose that ADAM-17 is part of a novel pro-angiogenic pathway leading to MMP-2 activation and vessel formation.
authors.affiliation: Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 912, Charleston, SC 29425, USA. goozp@musc.edu
authors.forename: Pal
authors.initials: P
authors.lastname: Göoz
authors.forename: Monika
authors.initials: M
authors.lastname: Göoz
authors.forename: Aleksander
authors.initials: A
authors.lastname: Baldys
authors.forename: Stanley
authors.initials: S
authors.lastname: Hoffman
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000502:physiology*; D000072198:ADAM17 Protein; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D014470:Umbilical Cord / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D042461:Vascular Endothelial Growth Factor A; D051722:ADAM Proteins; D020778:Matrix Metalloproteinase 2; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human