title: Microtubule-associated deacetylase HDAC6 promotes angiogenesis by regulating cell migration in an EB1-dependent manner.
abstract: Angiogenesis, a process by which the preexisting blood vasculature gives rise to new capillary vessels, is associated with a variety of physiologic and pathologic conditions. However, the molecular mechanism underlying this important process remains poorly understood. Here we show that histone deacetylase 6 (HDAC6), a microtubule-associated enzyme critical for cell motility, contributes to angiogenesis by regulating the polarization and migration of vascular endothelial cells. Inhibition of HDAC6 activity impairs the formation of new blood vessels in chick embryos and in angioreactors implanted in mice. The requirement for HDAC6 in angiogenesis is corroborated in vitro by analysis of endothelial tube formation and capillary sprouting. Our data further show that HDAC6 stimulates membrane ruffling at the leading edge to promote cell polarization. In addition, microtubule end binding protein 1 (EB1) is important for HDAC6 to exert its activity towards the migration of endothelial cells and generation of capillary-like structures. These results thus identify HDAC6 as a novel player in the angiogenic process and offer novel insights into the molecular mechanism governing endothelial cell migration and angiogenesis.
authors.affiliation: Department of Genetics and Cell Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
authors.forename: Songbo
authors.initials: S
authors.lastname: Xie
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ren
authors.forename: Lihong
authors.initials: L
authors.lastname: Huo
authors.forename: Jinmin
authors.initials: J
authors.lastname: Gao
authors.forename: Dandan
authors.initials: D
authors.lastname: Cui
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D042783:Endothelial Cells / Q000166:cytology; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism* / Q000502:physiology; D018919:Neovascularization, Physiologic
chemical_list: D000813:Anilides; C405804:EB1 microtubule binding proteins; D006877:Hydroxamic Acids; D008869:Microtubule-Associated Proteins; C474316:tubacin; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases