biostudies-literatureGooz PNCRR NIH HHSNIDDK NIH HHS33-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC2875258biostudies-literatureUnknown380(1)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 Biochemical and biophysical research communicationsADAM-17 regulates endothelial cell morphology, proliferation, and in vitro angiogenesis.PMC2875258P20 RR016434-096032K01 DK070054P20 RR016434K01 DK070054-05K01 DK070054-01Gooz MGooz PBaldys AHoffman SfalseADAM-17 regulates endothelial cell morphology, proliferation, and in vitro angiogenesis.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 2009-01-01T00:00:00Z2009 Feb2025-04-21T16:59:07.552Z2019-06-06T22:07:27ZS-EPMC28752581915034110.1016/j.bbrc.2009.01.013