title: Designed angiopoietin-1 variant, COMP-Ang1, protects against radiation-induced endothelial cell apoptosis.
abstract: Radiation therapy is a widely used cancer treatment, but it causes side effects even when localized radiotherapy is used. Extensive apoptosis of microvascular endothelial cells of the lamina propria is the primary lesion initiating intestinal radiation damage after abdominal radiation therapy. Many in vitro studies suggest that angiopoietin-1 (Ang1) has potential therapeutic applications in enhancing endothelial cell survival. For in vivo use, we developed a soluble, stable, and potent Ang1 variant, COMP-Ang1. COMP-Ang1 is more potent than native Ang1 in phosphorylating the Tie2 receptor in lung endothelial cells in vivo. Interestingly, COMP-Ang1 administered i.v. was mainly localized to microvascular endothelial cells of the intestinal villi and lung but not to microvascular endothelial cells of the liver. In irradiated mice, i.v. COMP-Ang1 protected against radiation-induced apoptosis in microcapillary endothelial cells of the intestinal villi and prolonged survival. Thus, COMP-Ang1 could be used as a therapeutic protein for specific protection against endothelial cell injury.
authors.affiliation: Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Cho
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kammerer
authors.forename: Hyuek Jong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Kunio
authors.initials: K
authors.lastname: Yasunaga
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Kim
authors.forename: Han-Ho
authors.initials: HH
authors.lastname: Choi
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
authors.forename: Gyun Min
authors.initials: GM
authors.lastname: Lee
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics* / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002196:Capillaries / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D064235:Matrilin Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D010766:Phosphorylation; D011832:Radiation Injuries / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D042787:Receptor, TIE-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D016019:Survival Analysis; D014018:Tissue Distribution
chemical_list: D042683:Angiopoietin-1; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C577540:Matn1 protein, mouse; D064235:Matrilin Proteins; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D042787:Receptor, TIE-2