title: Common and distinctive pathogenetic features of arteriovenous malformations in hereditary hemorrhagic telangiectasia 1 and hereditary hemorrhagic telangiectasia 2 animal models--brief report.
abstract: OBJECTIVE
  Hereditary hemorrhagic telangiectasia is a genetic disorder characterized by visceral and mucocutaneous arteriovenous malformations (AVMs). Clinically indistinguishable hereditary hemorrhagic telangiectasia 1 and hereditary hemorrhagic telangiectasia 2 are caused by mutations in ENG and ALK1, respectively. In this study, we have compared the development of visceral and mucocutaneous AVMs in adult stages between Eng- and Alk1-inducible knockout (iKO) models.
  
  
  RESULTS
  Eng or Alk1 were deleted from either vascular endothelial cells (ECs) or smooth muscle cells in adult stages using Scl-CreER and Myh11-CreER lines, respectively. Latex perfusion and intravital spectral imaging in a dorsal skinfold window chamber system were used to visualize remodeling vasculature during AVM formation. Global Eng deletion resulted in lethality with visceral AVMs and wound-induced skin AVMs. Deletion of Alk1 or Eng in ECs, but not in smooth muscle cells, resulted in wound-induced skin AVMs. Visceral AVMs were observed in EC-specific Alk1-iKO but not in Eng-iKO. Intravital spectral imaging revealed that Eng-iKO model exhibited more dynamic processes for AVM development when compared with Alk1-iKO model.
  
  
  CONCLUSIONS
  Both Alk1- and Eng-deficient models require a secondary insult, such as wounding, and ECs are the primary cell type responsible for the pathogenesis. However, Alk1 but not Eng deletion in ECs results in visceral AVMs.
authors.affiliation: From the Department of Physiology and Functional Genomics (E.M.G.-M., H.-L.N., T.A.C., S.-w.C., S.P.O.) and Department of Surgery (Z.J.), University of Florida, Gainesville; Department of Biomedical Engineering, Tongmyong University, Busan, Republic of Korea (S.-w.C.); Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (H.M.A.); and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea (Y.-J.L., S.P.O.).
authors.forename: Eva M
authors.initials: EM
authors.lastname: Garrido-Martin
authors.affiliation: From the Department of Physiology and Functional Genomics (E.M.G.-M., H.-L.N., T.A.C., S.-w.C., S.P.O.) and Department of Surgery (Z.J.), University of Florida, Gainesville; Department of Biomedical Engineering, Tongmyong University, Busan, Republic of Korea (S.-w.C.); Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (H.M.A.); and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea (Y.-J.L., S.P.O.).
authors.forename: Ha-Long
authors.initials: HL
authors.lastname: Nguyen
authors.affiliation: From the Department of Physiology and Functional Genomics (E.M.G.-M., H.-L.N., T.A.C., S.-w.C., S.P.O.) and Department of Surgery (Z.J.), University of Florida, Gainesville; Department of Biomedical Engineering, Tongmyong University, Busan, Republic of Korea (S.-w.C.); Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (H.M.A.); and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea (Y.-J.L., S.P.O.).
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Cunningham
authors.affiliation: From the Department of Physiology and Functional Genomics (E.M.G.-M., H.-L.N., T.A.C., S.-w.C., S.P.O.) and Department of Surgery (Z.J.), University of Florida, Gainesville; Department of Biomedical Engineering, Tongmyong University, Busan, Republic of Korea (S.-w.C.); Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (H.M.A.); and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea (Y.-J.L., S.P.O.).
authors.forename: Se-Woon
authors.initials: SW
authors.lastname: Choe
authors.affiliation: From the Department of Physiology and Functional Genomics (E.M.G.-M., H.-L.N., T.A.C., S.-w.C., S.P.O.) and Department of Surgery (Z.J.), University of Florida, Gainesville; Department of Biomedical Engineering, Tongmyong University, Busan, Republic of Korea (S.-w.C.); Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (H.M.A.); and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea (Y.-J.L., S.P.O.).
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: From the Department of Physiology and Functional Genomics (E.M.G.-M., H.-L.N., T.A.C., S.-w.C., S.P.O.) and Department of Surgery (Z.J.), University of Florida, Gainesville; Department of Biomedical Engineering, Tongmyong University, Busan, Republic of Korea (S.-w.C.); Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (H.M.A.); and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea (Y.-J.L., S.P.O.).
authors.forename: Helen M
authors.initials: HM
authors.lastname: Arthur
authors.affiliation: From the Department of Physiology and Functional Genomics (E.M.G.-M., H.-L.N., T.A.C., S.-w.C., S.P.O.) and Department of Surgery (Z.J.), University of Florida, Gainesville; Department of Biomedical Engineering, Tongmyong University, Busan, Republic of Korea (S.-w.C.); Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (H.M.A.); and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea (Y.-J.L., S.P.O.).
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: From the Department of Physiology and Functional Genomics (E.M.G.-M., H.-L.N., T.A.C., S.-w.C., S.P.O.) and Department of Surgery (Z.J.), University of Florida, Gainesville; Department of Biomedical Engineering, Tongmyong University, Busan, Republic of Korea (S.-w.C.); Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (H.M.A.); and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea (Y.-J.L., S.P.O.). ohp@ufl.edu.
authors.forename: S Paul
authors.initials: SP
authors.lastname: Oh
mesh_terms: D030201:Activin Receptors, Type I / Q000172:deficiency / Q000235:genetics; D030301:Activin Receptors, Type II; D000818:Animals; D001165:Arteriovenous Malformations / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000071063:Endoglin; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014945:Wound Healing
chemical_list: D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; C498931:Acvrl1 protein, mouse
keywords: Alk1 protein, mouse; arteriovenous malformations; endoglin protein, mouse; endothelial cells; myocytes, smooth muscle; telangiectasia, hereditary hemorrhagic