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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.
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
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
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