title: Differential angiogenic properties of lithium chloride in vitro and in vivo.
abstract: Wnt/β-catenin signaling induced by the Norrin/Frizzled-4 pathway has been shown to improve capillary repair following oxygen induced retinopathy (OIR) in the mouse, a model for retinopathy of prematurity. Here we investigated if treatment with the monovalent cation lithium that has been shown to augment Wnt/β-catenin signaling in vitro and in vivo has similar effects. In cultured human microvascular endothelial cells, LiCl as well as SB 216763, another small molecule that activates Wnt/β-catenin signaling, induced proliferation, survival and migration, which are all common parameters for angiogenic properties in vitro. Moreover, treatment with both agents caused an increase in the levels of β-catenin and their translocation to nuclei while quercetin, an inhibitor of Wnt/β-catenin signaling, completely blocked the effects of LiCl on proliferation. In mice with OIR, intraperitonal or intravitreal treatment with LiCl markedly increased the retinal levels of β-catenin, but did not improve capillary repair. In contrast, repair was significantly improved following intravitreal treatment with Norrin. The effects of LiCl on HDMEC in vitro have minor relevance for OIR in vivo, and the influence of the Norrin/Frizzled-4 pathway on capillary repair in OIR is not reproducible upon enhancing Wnt/β-catenin signaling by LiCl treatment strongly indicating the presence of additional and essential mechanisms.
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Ludwig F
authors.initials: LF
authors.lastname: Zeilbeck
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Müller
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Knobloch
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Tamm
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ohlmann
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020405:Dermis / Q000098:blood supply; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D018021:Lithium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D055806:Microvessels / Q000166:cytology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010100:Oxygen; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D005136:Eye Proteins; D007211:Indoles; D008301:Maleimides; C489916:Ndph protein, mouse; D009419:Nerve Tissue Proteins; C417521:SB 216763; D042461:Vascular Endothelial Growth Factor A; D018021:Lithium Chloride; D010100:Oxygen
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