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Common and Distinctive Pathogenetic Features of Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia 1 and Hereditary Hemorrhagic Telangiectasia 2 Animal Models-Brief Report

Lookup NU author(s): Professor Helen ArthurORCiD


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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.Approach and 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.

Publication metadata

Author(s): Garrido-Martin EM, Nguyen HL, Cunningham TA, Choe SW, Jiang ZH, Arthur HM, Lee YJ, Oh SP

Publication type: Article

Publication status: Published

Journal: Arteriosclerosis, Thrombosis and Vascular Biology

Year: 2014

Volume: 34

Issue: 10

Pages: 2232-2236

Print publication date: 01/10/2014

Online publication date: 31/07/2014

Acceptance date: 20/07/2014

ISSN (print): 1079-5642

ISSN (electronic): 1524-4636

Publisher: Lippincott Williams & Wilkins


DOI: 10.1161/ATVBAHA.114.303984


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Funder referenceFunder name
National Institute of Diabetes and Digestive and Kidney Diseases
12POST12030005American Heart Association
HL64024National Institutes of Health