Angiotensin receptor blockade mediated amelioration of mucopolysaccharidosis type I cardiac and craniofacial pathology.

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

SUBMITTER: Osborn MJ 

PROVIDER: S-EPMC5335863 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature