Angiotensin receptor blockade mediated amelioration of mucopolysaccharidosis type I cardiac and craniofacial pathology View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-10-14

AUTHORS

Mark J. Osborn, Beau R. Webber, Ronald T. McElmurry, Kyle D. Rudser, Anthony P. DeFeo, Michael Muradian, Anna Petryk, Benedikt Hallgrimsson, Bruce R. Blazar, Jakub Tolar, Elizabeth A. Braunlin

ABSTRACT

Mucopolysaccharidosis type I (MPS IH) is a lysosomal storage disease (LSD) caused by inactivating mutations to the alpha-L-iduronidase (IDUA) gene. Treatment focuses on IDUA enzyme replacement and currently employed methods can be non-uniform in their efficacy particularly for the cardiac and craniofacial pathology. Therefore, we undertook efforts to better define the pathological cascade accounting for treatment refractory manifestations and demonstrate a role for the renin angiotensin system (RAS) using the IDUA−/− mouse model. Perturbation of the RAS in the aorta was more profound in male animals suggesting a causative role in the observed gender dimorphism and angiotensin receptor blockade (ARB) resulted in improved cardiac function. Further, we show the ability of losartan to prevent shortening of the snout, a common craniofacial anomaly in IDUA−/− mice. These data show a key role for the RAS in MPS associated pathology and support the inclusion of losartan as an augmentation to current therapies. More... »

PAGES

281-289

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10545-016-9988-z

DOI

http://dx.doi.org/10.1007/s10545-016-9988-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1002977857

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27743312


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